Conference Coverage

A claim that drinking tea might protect people against developing type 2 diabetes has been met with caution from multiple experts ahead of the annual meeting of the European Association for the Study of Diabetes.

The claim is that people who drink four or more cups of tea every day – specifically green, Oolong, or black tea – are 17% less likely to develop type 2 diabetes than those who do not drink tea. Drinking fewer cups of tea per day was not found to confer any benefit.

“Our results are exciting because they suggest that people can do something as simple as drinking four cups of tea a day to potentially lessen their risk of developing type 2 diabetes,” Xiaying Li of Wuhan (China) University of Science and Technology is quoted as saying in an official EASD press release.

NataliTerr/Fotolia.com

“It is possible that particular components in tea, such as polyphenols, may reduce blood glucose levels, but a sufficient amount of these bioactive compounds may be needed to be effective,” Dr. Li added.

“The words ‘suggest’ and ‘potentially’ are crucial here,” said Kevin McConway, PhD, MSc, MBA, emeritus professor of applied statistics at The Open University, said in a separate statement to the press that reeled in Dr. Li’s enthusiasm.

“Tea drinking would only be useful for reducing diabetes risk if the tea drinking causes reductions in risk, that is, if the risk is reduced if you drink the tea and not if you don’t – and this study simply can’t show whether it does this or not,” Dr. Conway stressed.

Naveed Sattar, FMedSci FRCPath FRCPGlas FRSE, professor of metabolic medicine at the University of Glasgow, was also cautiously critical. “There is no good trial evidence whatsoever that the chemicals in tea prevent diabetes,” he observed separately.

“So, I suspect its more about tea being healthier (less calorific) than many alternative drinks or tea drinkers leading healthier lives more generally.”

Dr. Sattar added that it could be that people who drink tea might also be avoiding drinking more harmful sugary drinks and have other health behaviors that might lead them to have a lower risk for type 2 diabetes.

Time for tea?

Dr. Li will present the findings of two analyses on Sept. 21 at the EASD meeting: the first a large observational cohort study and the second an updated systematic review and meta-analysis.

For the cohort study, Dr. Li and her coauthors took data on more than 5,100 adults who had participated in the long-running and ongoing China Health and Nutrition Survey (CHNS). Information on tea drinking behavior was extracted from questionnaires that had been filled out at two time points – 1997 and 2009 – and they determined whether people had developed type 2 diabetes according to American Diabetes Association criteria.

Nearly half, 45.8%, were found to be tea drinkers, and 10% of the population they sampled had developed type 2 diabetes. No association between tea drinking and type 2 diabetes development was found, however, with the hazard ratio comparing tea drinkers and non–tea drinkers sitting firmly at 1.02. Moreover, a sensitivity analysis that excluded participants who had developed type 2 diabetes in the first 3 years of follow-up did not change the result.

Things were slightly different when Dr. Li and associates performed their meta-analysis that involved analyzing data on more than 1 million participants in 19 studies conducted in eight countries that had been published up to September 2021.

Here, they found there was a significant (P < .003) linear association between tea consumption and having type 2 diabetes, with the relative risk of developing type 2 diabetes decreasing by 0.986 for every additional cup of tea that was drunk.

HRs for the development of type 2 diabetes in tea drinkers versus non–tea drinkers were 1.00 for those who drank less than one cup per day, 0.96 for those who had one to two cups, and 0.84 for those who drank four or more cups.

“While more research needs to be done to determine the exact dosage and mechanisms behind these observations, our findings suggest that drinking tea is beneficial in reducing the risk of type 2 diabetes, but only at high doses (at least 4 cups a day)”, said Dr. Li.

Perhaps, “we did not find an association between tea drinking and type 2 diabetes in our cohort study because we did not look at higher tea consumption,” she added.

Tempest in a teacup

“This is large, observational data. It’s not a randomized controlled trial so there’s plenty of room for data to be misunderstood,” warned Matt Sydes, MSc, professor of clinical trials & methodology at the MRC Clinical Trials Unit, University College London.

“Everyone drinks fluids. If there is an effect here (and that’s a big if), it might be not about the tea they drink, but about what they don’t drink. One can’t tell at the moment. It seems unlikely that a large randomized controlled trial could be done to disambiguate” added Dr. Sydes

“Being only a conference abstract, it is difficult to assess the quality of this research,” Baptiste Leurent, PhD, a medical statistician also working at University College London, said. Not only was the cohort study observational, so were all the other studies included in the meta-analysis, he pointed out.

“Therefore, no cause-effect conclusions can be drawn. The association could simply be due to other factors, such as those drinking more tea having a healthier lifestyle. It does not seem that the authors tried to control for confounders, which is usually difficult in meta-analysis,” Dr. Leurent said.

“There is reason to be a bit skeptical at this point; we really need to have the full details to assess it properly,” said Jonathan Cook of the Centre for Statistics in Medicine at the University of Oxford (England). “It’s a fair attempt to look at this, but not cutting edge, [using] fairly standard approaches.”

Similar studies have shown a reduced risk associated with coffee drinking, noted Duane Mellor, PhD, a registered dietitian and senior teaching fellow at Aston University in Birmingham.

“The important take-home message is that lifestyle is important in managing risk of developing type 2 diabetes,” Dr. Mellor said.

“That includes choosing low-calorie drinks including mainly water as well as unsweetened tea and coffee as your drinks of choice as part of a healthy lifestyle.”

The study was funded by the Young Talents Project of Hubei Provincial Health Commission, the Science and Technology Research Key Project of Education Department of Hubei Province, the Sanuo Diabetes Charity Foundation, and the Xiangyang Science and Technology Plan Project, all based in China. Dr. Li had no conflicts of interest to disclose. Dr. McConway is a Trustee and on the advisory committee of The Science Media Centre.  Dr. Sattar has consulted for many companies that make diabetes and cardiovascular drugs and has been involved in multiple trials of lifestyle approaches for the prevention and remission of diabetes. Dr. Sydes, Dr. Leurent, Dr. Cook, and Dr. Mellor had no conflicts of interest to report.

A claim that drinking tea might protect people against developing type 2 diabetes has been met with caution from multiple experts ahead of the annual meeting of the European Association for the Study of Diabetes.

The claim is that people who drink four or more cups of tea every day – specifically green, Oolong, or black tea – are 17% less likely to develop type 2 diabetes than those who do not drink tea. Drinking fewer cups of tea per day was not found to confer any benefit.

“Our results are exciting because they suggest that people can do something as simple as drinking four cups of tea a day to potentially lessen their risk of developing type 2 diabetes,” Xiaying Li of Wuhan (China) University of Science and Technology is quoted as saying in an official EASD press release.

NataliTerr/Fotolia.com

“It is possible that particular components in tea, such as polyphenols, may reduce blood glucose levels, but a sufficient amount of these bioactive compounds may be needed to be effective,” Dr. Li added.

“The words ‘suggest’ and ‘potentially’ are crucial here,” said Kevin McConway, PhD, MSc, MBA, emeritus professor of applied statistics at The Open University, said in a separate statement to the press that reeled in Dr. Li’s enthusiasm.

“Tea drinking would only be useful for reducing diabetes risk if the tea drinking causes reductions in risk, that is, if the risk is reduced if you drink the tea and not if you don’t – and this study simply can’t show whether it does this or not,” Dr. Conway stressed.

Naveed Sattar, FMedSci FRCPath FRCPGlas FRSE, professor of metabolic medicine at the University of Glasgow, was also cautiously critical. “There is no good trial evidence whatsoever that the chemicals in tea prevent diabetes,” he observed separately.

“So, I suspect its more about tea being healthier (less calorific) than many alternative drinks or tea drinkers leading healthier lives more generally.”

Dr. Sattar added that it could be that people who drink tea might also be avoiding drinking more harmful sugary drinks and have other health behaviors that might lead them to have a lower risk for type 2 diabetes.

Time for tea?

Dr. Li will present the findings of two analyses on Sept. 21 at the EASD meeting: the first a large observational cohort study and the second an updated systematic review and meta-analysis.

For the cohort study, Dr. Li and her coauthors took data on more than 5,100 adults who had participated in the long-running and ongoing China Health and Nutrition Survey (CHNS). Information on tea drinking behavior was extracted from questionnaires that had been filled out at two time points – 1997 and 2009 – and they determined whether people had developed type 2 diabetes according to American Diabetes Association criteria.

Nearly half, 45.8%, were found to be tea drinkers, and 10% of the population they sampled had developed type 2 diabetes. No association between tea drinking and type 2 diabetes development was found, however, with the hazard ratio comparing tea drinkers and non–tea drinkers sitting firmly at 1.02. Moreover, a sensitivity analysis that excluded participants who had developed type 2 diabetes in the first 3 years of follow-up did not change the result.

Things were slightly different when Dr. Li and associates performed their meta-analysis that involved analyzing data on more than 1 million participants in 19 studies conducted in eight countries that had been published up to September 2021.

Here, they found there was a significant (P < .003) linear association between tea consumption and having type 2 diabetes, with the relative risk of developing type 2 diabetes decreasing by 0.986 for every additional cup of tea that was drunk.

HRs for the development of type 2 diabetes in tea drinkers versus non–tea drinkers were 1.00 for those who drank less than one cup per day, 0.96 for those who had one to two cups, and 0.84 for those who drank four or more cups.

“While more research needs to be done to determine the exact dosage and mechanisms behind these observations, our findings suggest that drinking tea is beneficial in reducing the risk of type 2 diabetes, but only at high doses (at least 4 cups a day)”, said Dr. Li.

Perhaps, “we did not find an association between tea drinking and type 2 diabetes in our cohort study because we did not look at higher tea consumption,” she added.

Tempest in a teacup

“This is large, observational data. It’s not a randomized controlled trial so there’s plenty of room for data to be misunderstood,” warned Matt Sydes, MSc, professor of clinical trials & methodology at the MRC Clinical Trials Unit, University College London.

“Everyone drinks fluids. If there is an effect here (and that’s a big if), it might be not about the tea they drink, but about what they don’t drink. One can’t tell at the moment. It seems unlikely that a large randomized controlled trial could be done to disambiguate” added Dr. Sydes

“Being only a conference abstract, it is difficult to assess the quality of this research,” Baptiste Leurent, PhD, a medical statistician also working at University College London, said. Not only was the cohort study observational, so were all the other studies included in the meta-analysis, he pointed out.

“Therefore, no cause-effect conclusions can be drawn. The association could simply be due to other factors, such as those drinking more tea having a healthier lifestyle. It does not seem that the authors tried to control for confounders, which is usually difficult in meta-analysis,” Dr. Leurent said.

“There is reason to be a bit skeptical at this point; we really need to have the full details to assess it properly,” said Jonathan Cook of the Centre for Statistics in Medicine at the University of Oxford (England). “It’s a fair attempt to look at this, but not cutting edge, [using] fairly standard approaches.”

Similar studies have shown a reduced risk associated with coffee drinking, noted Duane Mellor, PhD, a registered dietitian and senior teaching fellow at Aston University in Birmingham.

“The important take-home message is that lifestyle is important in managing risk of developing type 2 diabetes,” Dr. Mellor said.

“That includes choosing low-calorie drinks including mainly water as well as unsweetened tea and coffee as your drinks of choice as part of a healthy lifestyle.”

The study was funded by the Young Talents Project of Hubei Provincial Health Commission, the Science and Technology Research Key Project of Education Department of Hubei Province, the Sanuo Diabetes Charity Foundation, and the Xiangyang Science and Technology Plan Project, all based in China. Dr. Li had no conflicts of interest to disclose. Dr. McConway is a Trustee and on the advisory committee of The Science Media Centre.  Dr. Sattar has consulted for many companies that make diabetes and cardiovascular drugs and has been involved in multiple trials of lifestyle approaches for the prevention and remission of diabetes. Dr. Sydes, Dr. Leurent, Dr. Cook, and Dr. Mellor had no conflicts of interest to report.

A claim that drinking tea might protect people against developing type 2 diabetes has been met with caution from multiple experts ahead of the annual meeting of the European Association for the Study of Diabetes.

The claim is that people who drink four or more cups of tea every day – specifically green, Oolong, or black tea – are 17% less likely to develop type 2 diabetes than those who do not drink tea. Drinking fewer cups of tea per day was not found to confer any benefit.

“Our results are exciting because they suggest that people can do something as simple as drinking four cups of tea a day to potentially lessen their risk of developing type 2 diabetes,” Xiaying Li of Wuhan (China) University of Science and Technology is quoted as saying in an official EASD press release.

NataliTerr/Fotolia.com

“It is possible that particular components in tea, such as polyphenols, may reduce blood glucose levels, but a sufficient amount of these bioactive compounds may be needed to be effective,” Dr. Li added.

“The words ‘suggest’ and ‘potentially’ are crucial here,” said Kevin McConway, PhD, MSc, MBA, emeritus professor of applied statistics at The Open University, said in a separate statement to the press that reeled in Dr. Li’s enthusiasm.

“Tea drinking would only be useful for reducing diabetes risk if the tea drinking causes reductions in risk, that is, if the risk is reduced if you drink the tea and not if you don’t – and this study simply can’t show whether it does this or not,” Dr. Conway stressed.

Naveed Sattar, FMedSci FRCPath FRCPGlas FRSE, professor of metabolic medicine at the University of Glasgow, was also cautiously critical. “There is no good trial evidence whatsoever that the chemicals in tea prevent diabetes,” he observed separately.

“So, I suspect its more about tea being healthier (less calorific) than many alternative drinks or tea drinkers leading healthier lives more generally.”

Dr. Sattar added that it could be that people who drink tea might also be avoiding drinking more harmful sugary drinks and have other health behaviors that might lead them to have a lower risk for type 2 diabetes.

Time for tea?

Dr. Li will present the findings of two analyses on Sept. 21 at the EASD meeting: the first a large observational cohort study and the second an updated systematic review and meta-analysis.

For the cohort study, Dr. Li and her coauthors took data on more than 5,100 adults who had participated in the long-running and ongoing China Health and Nutrition Survey (CHNS). Information on tea drinking behavior was extracted from questionnaires that had been filled out at two time points – 1997 and 2009 – and they determined whether people had developed type 2 diabetes according to American Diabetes Association criteria.

Nearly half, 45.8%, were found to be tea drinkers, and 10% of the population they sampled had developed type 2 diabetes. No association between tea drinking and type 2 diabetes development was found, however, with the hazard ratio comparing tea drinkers and non–tea drinkers sitting firmly at 1.02. Moreover, a sensitivity analysis that excluded participants who had developed type 2 diabetes in the first 3 years of follow-up did not change the result.

Things were slightly different when Dr. Li and associates performed their meta-analysis that involved analyzing data on more than 1 million participants in 19 studies conducted in eight countries that had been published up to September 2021.

Here, they found there was a significant (P < .003) linear association between tea consumption and having type 2 diabetes, with the relative risk of developing type 2 diabetes decreasing by 0.986 for every additional cup of tea that was drunk.

HRs for the development of type 2 diabetes in tea drinkers versus non–tea drinkers were 1.00 for those who drank less than one cup per day, 0.96 for those who had one to two cups, and 0.84 for those who drank four or more cups.

“While more research needs to be done to determine the exact dosage and mechanisms behind these observations, our findings suggest that drinking tea is beneficial in reducing the risk of type 2 diabetes, but only at high doses (at least 4 cups a day)”, said Dr. Li.

Perhaps, “we did not find an association between tea drinking and type 2 diabetes in our cohort study because we did not look at higher tea consumption,” she added.

Tempest in a teacup

“This is large, observational data. It’s not a randomized controlled trial so there’s plenty of room for data to be misunderstood,” warned Matt Sydes, MSc, professor of clinical trials & methodology at the MRC Clinical Trials Unit, University College London.

“Everyone drinks fluids. If there is an effect here (and that’s a big if), it might be not about the tea they drink, but about what they don’t drink. One can’t tell at the moment. It seems unlikely that a large randomized controlled trial could be done to disambiguate” added Dr. Sydes

“Being only a conference abstract, it is difficult to assess the quality of this research,” Baptiste Leurent, PhD, a medical statistician also working at University College London, said. Not only was the cohort study observational, so were all the other studies included in the meta-analysis, he pointed out.

“Therefore, no cause-effect conclusions can be drawn. The association could simply be due to other factors, such as those drinking more tea having a healthier lifestyle. It does not seem that the authors tried to control for confounders, which is usually difficult in meta-analysis,” Dr. Leurent said.

“There is reason to be a bit skeptical at this point; we really need to have the full details to assess it properly,” said Jonathan Cook of the Centre for Statistics in Medicine at the University of Oxford (England). “It’s a fair attempt to look at this, but not cutting edge, [using] fairly standard approaches.”

Similar studies have shown a reduced risk associated with coffee drinking, noted Duane Mellor, PhD, a registered dietitian and senior teaching fellow at Aston University in Birmingham.

“The important take-home message is that lifestyle is important in managing risk of developing type 2 diabetes,” Dr. Mellor said.

“That includes choosing low-calorie drinks including mainly water as well as unsweetened tea and coffee as your drinks of choice as part of a healthy lifestyle.”

The study was funded by the Young Talents Project of Hubei Provincial Health Commission, the Science and Technology Research Key Project of Education Department of Hubei Province, the Sanuo Diabetes Charity Foundation, and the Xiangyang Science and Technology Plan Project, all based in China. Dr. Li had no conflicts of interest to disclose. Dr. McConway is a Trustee and on the advisory committee of The Science Media Centre.  Dr. Sattar has consulted for many companies that make diabetes and cardiovascular drugs and has been involved in multiple trials of lifestyle approaches for the prevention and remission of diabetes. Dr. Sydes, Dr. Leurent, Dr. Cook, and Dr. Mellor had no conflicts of interest to report.

Highlights of the European Association for the Study of Diabetes 2022 annual meeting include new data on weight loss with the blockbuster twincretin tirzepatide and on the effects of dapagliflozin on heart failure in people with diabetes, as well as updated guidelines for type 2 diabetes management.

The EASD meeting will take place Sept. 19-23 in Stockholm. It will be the first in-person meeting since 2019 but will also feature live-streamed content for participants around the world.

“The EASD congress will cover all the different areas and aspects of diabetes research – clinical, basic, epidemiologic, and psychological,” EASD President Stefano Del Prato, MD, told this news organization.

What attendees should expect, said Del Prato of the University of Pisa (Italy), “is the pleasure to be able to participate in person at a meeting and get useful information, not only in terms of the knowledge and intellectual aspects of diabetes, but also something that can be implemented the following day in their daily clinical activities.”  

EASD Honorary Secretary Mikael Rydén, MD, added: “I think meeting attendees will really be able to get the absolutely latest developments in all the areas that are relevant to diabetes treatments. It’s the best way to keep yourself up to date.”

This year, in particular, there’s a focus on past, present, and future trends in type 2 diabetes management, along with the co-occurring conditions of obesity, heart failure, and metabolic fatty liver disease.  
 

DELIVER: The diabetes side

On Sept. 22, new data will be presented from the DELIVER trial on the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) in patients with heart failure with preserved ejection fraction, comparing data for participants with diabetes, prediabetes, and normoglycemia.

Primary results from DELIVER were presented Aug. 26 at the European Society of Cardiology Congress 2022 in Barcelona and simultaneously published in the New England Journal of Medicine. The results showed that dapagliflozin benefits patients with heart failure with preserved ejection fraction, as previously demonstrated in those with reduced ejection fraction in the DAPA-HF trial.

“This information is quite important and is becoming of major interest in the field of diabetes,” Dr. Del Prato said, adding that a related joint EASD/ESC symposium will take place the next morning, on Sept. 23, entitled, “New perspectives on heart function and failure in diabetes.”

“So, within the congress, you get the background, pathophysiology, the diagnostic aspects, and the results of the effect of dapagliflozin on those individuals.”

Dr. Rydén commented, “I think this underlines how important it is for diabetologists to screen our patients better for heart failure because we can actually treat them now.”

However, Dr. Rydén of the Karolinska Institute, Stockholm, also cautioned about use of SGLT2 inhibitors in people with diabetes who use insulin, given the risk of euglycemic diabetic ketoacidosis. “These drugs have side effects and you have to be wary who you prescribe them to. For those on multiple daily [insulin] injections, the side effects probably outweigh the benefits.”
 

Tirzepatide, weight loss, and type 2 diabetes remission

On Sept. 21, a symposium will provide new data for the dual glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide, approved for the treatment of type 2 diabetes in the United States in May with the brand name Mounjaro. The agent is now being studied as an obesity treatment.

Data from the SURMOUNT-1 trial presented at the ADA meeting in June showed the drug produced “unprecedented” weight loss of up to 22.5%.

At EASD, those findings will be reviewed and new data presented on morbidity and mortality, along with a new commentary. The degree of weight loss seen with this new twincretin has furthered discussion about the concept of remission in type 2 diabetes, Dr. Rydén noted. That will also be the subject of the Diabetologia symposium on Sept. 21, entitled, “Remission of type 2 diabetes – fact or fiction?”

Regarding tirzepatide, Dr. Rydén said: “It’s amazing, the most powerful antiobesity drug we have at our disposal. These drugs slow gastric emptying and have other beneficial effects. … We’re now closing in on drugs that produce more than 15% weight loss. That appears to be the ‘magic bullet’ where you can achieve type 2 diabetes remission.” He pointed to a symposium sponsored by The Lancet on this topic at last year’s EASD meeting.

“I think what we want with our drugs is not to treat but actually to combat type 2 diabetes and really to achieve remission. Of course, if you’ve had it for many decades that might be impossible, but we know that particularly in the first 5-10 years it’s very important to have good glucose control and we know we can also achieve remission.”

Dr. Del Prato noted the importance of weight reduction at the time of type 2 diabetes diagnosis will be emphasized in the ADA/EASD consensus document on the management of hyperglycemia in type 2 diabetes, to be presented in its final form on Sept. 23.

“I think we’ll be learning more about potential remission in the future, both because of metabolic surgery and agents like tirzepatide. The reduction in body weight that can be achieved [with these newer drugs], or that has been reported so far, is the closest to what can be obtained with metabolic surgery. I think there will be more and more information and a lot of discussion about this, and of course about the definition of remission and what to do after remission has occurred,” Dr. Del Prato said.  

The revised ADA/EASD consensus document is expected to endorse weight loss as a “co-primary goal” of care for those without cardiorenal disease, along with early initiation of combination therapies – for example, taking two drugs immediately upon diagnosis, rather than just metformin – as opposed to the prior stepwise approach. The document will also cover use of newer glucose-lowering therapies, surgery, and behavioral interventions.  

The key is a holistic approach, Dr. Del Prato said. “Of course, glucose control is important, but it’s not the only thing. The heterogeneity of the population with diabetes is also important. Some may already have microvascular complications, kidney dysfunction, are more or less obese, and older or younger. We need to keep these differences in mind to provide more and more individualized treatment.”

Related to that, he noted, will be a joint EASD/ADA symposium on Sept. 19, entitled, “Precision medicine in type 2 diabetes: How far can we get?”
 

COVID-19 and diabetes, UKPDS, type 1 diabetes, and much more

As always, there’s a whole lot more. On Sept. 21, there will be a symposium on COVID-19 and diabetes.

Another, on diabetes technology, has a somewhat cautionary theme: “A new hope (Star Wars) or strange new worlds (Star Trek): Submerging diabetes into emerging technologies.” One of the speakers will address the question: “Are we becoming robots? Automated insulin delivery (AID) systems for everyone with type 1 diabetes: Strengths and limitations.” And this year’s EASD/JDRF symposium topic will be prevention of type 1 diabetes.

Yet another symposium on Sept. 21 will present 44-year follow-up data from the landmark United Kingdom Prospective Diabetes Study (UKPDS), including an economic analysis and a look at dementia outcomes. “It’s a historical thing. This big trial represents a gold mine of information,” Dr. Del Prato commented.

On Sept. 22, new data will be presented for the investigational once-weekly insulins during a symposium entitled, “Re-inventing the insulin experience: Exploring the prospects of once-weekly insulins.”

And lest anyone was thinking of leaving the conference early, there’s a full agenda on Sept. 23, including symposia on diabetic nephropathy, type 1 diabetes, diabetes in old age, dietary management, and the role of primary care, among others. There will also be 12 separate oral presentation sessions that day.

Overall, the meeting will reflect the multidisciplinary direction the field is headed, Dr. Rydén said.

“We’re still in an era of medicine where a lot of things happen every year. Now we have the next generation of drugs that are coming that combine many areas of treatment – obesity, cardiology, and nephrology. So, we’re integrating. The future is integrating the diabetes world with our friends in other areas of clinical medicine.”

Dr. Del Prato has reported being a consultant, advisory board member, and/or lecturer for AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Sanofi, Takeda, Eli Lilly, Abbott, and Applied Therapeutics. Dr. Rydén has reported receiving lecture fees from the Novo Nordisk Foundation and serving on advisory boards for MSD, Lilly, Boehringer Ingelheim, and AstraZeneca.

A version of this article first appeared on Medscape.com.  
 

Highlights of the European Association for the Study of Diabetes 2022 annual meeting include new data on weight loss with the blockbuster twincretin tirzepatide and on the effects of dapagliflozin on heart failure in people with diabetes, as well as updated guidelines for type 2 diabetes management.

The EASD meeting will take place Sept. 19-23 in Stockholm. It will be the first in-person meeting since 2019 but will also feature live-streamed content for participants around the world.

“The EASD congress will cover all the different areas and aspects of diabetes research – clinical, basic, epidemiologic, and psychological,” EASD President Stefano Del Prato, MD, told this news organization.

What attendees should expect, said Del Prato of the University of Pisa (Italy), “is the pleasure to be able to participate in person at a meeting and get useful information, not only in terms of the knowledge and intellectual aspects of diabetes, but also something that can be implemented the following day in their daily clinical activities.”  

EASD Honorary Secretary Mikael Rydén, MD, added: “I think meeting attendees will really be able to get the absolutely latest developments in all the areas that are relevant to diabetes treatments. It’s the best way to keep yourself up to date.”

This year, in particular, there’s a focus on past, present, and future trends in type 2 diabetes management, along with the co-occurring conditions of obesity, heart failure, and metabolic fatty liver disease.  
 

DELIVER: The diabetes side

On Sept. 22, new data will be presented from the DELIVER trial on the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) in patients with heart failure with preserved ejection fraction, comparing data for participants with diabetes, prediabetes, and normoglycemia.

Primary results from DELIVER were presented Aug. 26 at the European Society of Cardiology Congress 2022 in Barcelona and simultaneously published in the New England Journal of Medicine. The results showed that dapagliflozin benefits patients with heart failure with preserved ejection fraction, as previously demonstrated in those with reduced ejection fraction in the DAPA-HF trial.

“This information is quite important and is becoming of major interest in the field of diabetes,” Dr. Del Prato said, adding that a related joint EASD/ESC symposium will take place the next morning, on Sept. 23, entitled, “New perspectives on heart function and failure in diabetes.”

“So, within the congress, you get the background, pathophysiology, the diagnostic aspects, and the results of the effect of dapagliflozin on those individuals.”

Dr. Rydén commented, “I think this underlines how important it is for diabetologists to screen our patients better for heart failure because we can actually treat them now.”

However, Dr. Rydén of the Karolinska Institute, Stockholm, also cautioned about use of SGLT2 inhibitors in people with diabetes who use insulin, given the risk of euglycemic diabetic ketoacidosis. “These drugs have side effects and you have to be wary who you prescribe them to. For those on multiple daily [insulin] injections, the side effects probably outweigh the benefits.”
 

Tirzepatide, weight loss, and type 2 diabetes remission

On Sept. 21, a symposium will provide new data for the dual glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide, approved for the treatment of type 2 diabetes in the United States in May with the brand name Mounjaro. The agent is now being studied as an obesity treatment.

Data from the SURMOUNT-1 trial presented at the ADA meeting in June showed the drug produced “unprecedented” weight loss of up to 22.5%.

At EASD, those findings will be reviewed and new data presented on morbidity and mortality, along with a new commentary. The degree of weight loss seen with this new twincretin has furthered discussion about the concept of remission in type 2 diabetes, Dr. Rydén noted. That will also be the subject of the Diabetologia symposium on Sept. 21, entitled, “Remission of type 2 diabetes – fact or fiction?”

Regarding tirzepatide, Dr. Rydén said: “It’s amazing, the most powerful antiobesity drug we have at our disposal. These drugs slow gastric emptying and have other beneficial effects. … We’re now closing in on drugs that produce more than 15% weight loss. That appears to be the ‘magic bullet’ where you can achieve type 2 diabetes remission.” He pointed to a symposium sponsored by The Lancet on this topic at last year’s EASD meeting.

“I think what we want with our drugs is not to treat but actually to combat type 2 diabetes and really to achieve remission. Of course, if you’ve had it for many decades that might be impossible, but we know that particularly in the first 5-10 years it’s very important to have good glucose control and we know we can also achieve remission.”

Dr. Del Prato noted the importance of weight reduction at the time of type 2 diabetes diagnosis will be emphasized in the ADA/EASD consensus document on the management of hyperglycemia in type 2 diabetes, to be presented in its final form on Sept. 23.

“I think we’ll be learning more about potential remission in the future, both because of metabolic surgery and agents like tirzepatide. The reduction in body weight that can be achieved [with these newer drugs], or that has been reported so far, is the closest to what can be obtained with metabolic surgery. I think there will be more and more information and a lot of discussion about this, and of course about the definition of remission and what to do after remission has occurred,” Dr. Del Prato said.  

The revised ADA/EASD consensus document is expected to endorse weight loss as a “co-primary goal” of care for those without cardiorenal disease, along with early initiation of combination therapies – for example, taking two drugs immediately upon diagnosis, rather than just metformin – as opposed to the prior stepwise approach. The document will also cover use of newer glucose-lowering therapies, surgery, and behavioral interventions.  

The key is a holistic approach, Dr. Del Prato said. “Of course, glucose control is important, but it’s not the only thing. The heterogeneity of the population with diabetes is also important. Some may already have microvascular complications, kidney dysfunction, are more or less obese, and older or younger. We need to keep these differences in mind to provide more and more individualized treatment.”

Related to that, he noted, will be a joint EASD/ADA symposium on Sept. 19, entitled, “Precision medicine in type 2 diabetes: How far can we get?”
 

COVID-19 and diabetes, UKPDS, type 1 diabetes, and much more

As always, there’s a whole lot more. On Sept. 21, there will be a symposium on COVID-19 and diabetes.

Another, on diabetes technology, has a somewhat cautionary theme: “A new hope (Star Wars) or strange new worlds (Star Trek): Submerging diabetes into emerging technologies.” One of the speakers will address the question: “Are we becoming robots? Automated insulin delivery (AID) systems for everyone with type 1 diabetes: Strengths and limitations.” And this year’s EASD/JDRF symposium topic will be prevention of type 1 diabetes.

Yet another symposium on Sept. 21 will present 44-year follow-up data from the landmark United Kingdom Prospective Diabetes Study (UKPDS), including an economic analysis and a look at dementia outcomes. “It’s a historical thing. This big trial represents a gold mine of information,” Dr. Del Prato commented.

On Sept. 22, new data will be presented for the investigational once-weekly insulins during a symposium entitled, “Re-inventing the insulin experience: Exploring the prospects of once-weekly insulins.”

And lest anyone was thinking of leaving the conference early, there’s a full agenda on Sept. 23, including symposia on diabetic nephropathy, type 1 diabetes, diabetes in old age, dietary management, and the role of primary care, among others. There will also be 12 separate oral presentation sessions that day.

Overall, the meeting will reflect the multidisciplinary direction the field is headed, Dr. Rydén said.

“We’re still in an era of medicine where a lot of things happen every year. Now we have the next generation of drugs that are coming that combine many areas of treatment – obesity, cardiology, and nephrology. So, we’re integrating. The future is integrating the diabetes world with our friends in other areas of clinical medicine.”

Dr. Del Prato has reported being a consultant, advisory board member, and/or lecturer for AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Sanofi, Takeda, Eli Lilly, Abbott, and Applied Therapeutics. Dr. Rydén has reported receiving lecture fees from the Novo Nordisk Foundation and serving on advisory boards for MSD, Lilly, Boehringer Ingelheim, and AstraZeneca.

A version of this article first appeared on Medscape.com.  
 

Highlights of the European Association for the Study of Diabetes 2022 annual meeting include new data on weight loss with the blockbuster twincretin tirzepatide and on the effects of dapagliflozin on heart failure in people with diabetes, as well as updated guidelines for type 2 diabetes management.

The EASD meeting will take place Sept. 19-23 in Stockholm. It will be the first in-person meeting since 2019 but will also feature live-streamed content for participants around the world.

“The EASD congress will cover all the different areas and aspects of diabetes research – clinical, basic, epidemiologic, and psychological,” EASD President Stefano Del Prato, MD, told this news organization.

What attendees should expect, said Del Prato of the University of Pisa (Italy), “is the pleasure to be able to participate in person at a meeting and get useful information, not only in terms of the knowledge and intellectual aspects of diabetes, but also something that can be implemented the following day in their daily clinical activities.”  

EASD Honorary Secretary Mikael Rydén, MD, added: “I think meeting attendees will really be able to get the absolutely latest developments in all the areas that are relevant to diabetes treatments. It’s the best way to keep yourself up to date.”

This year, in particular, there’s a focus on past, present, and future trends in type 2 diabetes management, along with the co-occurring conditions of obesity, heart failure, and metabolic fatty liver disease.  
 

DELIVER: The diabetes side

On Sept. 22, new data will be presented from the DELIVER trial on the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) in patients with heart failure with preserved ejection fraction, comparing data for participants with diabetes, prediabetes, and normoglycemia.

Primary results from DELIVER were presented Aug. 26 at the European Society of Cardiology Congress 2022 in Barcelona and simultaneously published in the New England Journal of Medicine. The results showed that dapagliflozin benefits patients with heart failure with preserved ejection fraction, as previously demonstrated in those with reduced ejection fraction in the DAPA-HF trial.

“This information is quite important and is becoming of major interest in the field of diabetes,” Dr. Del Prato said, adding that a related joint EASD/ESC symposium will take place the next morning, on Sept. 23, entitled, “New perspectives on heart function and failure in diabetes.”

“So, within the congress, you get the background, pathophysiology, the diagnostic aspects, and the results of the effect of dapagliflozin on those individuals.”

Dr. Rydén commented, “I think this underlines how important it is for diabetologists to screen our patients better for heart failure because we can actually treat them now.”

However, Dr. Rydén of the Karolinska Institute, Stockholm, also cautioned about use of SGLT2 inhibitors in people with diabetes who use insulin, given the risk of euglycemic diabetic ketoacidosis. “These drugs have side effects and you have to be wary who you prescribe them to. For those on multiple daily [insulin] injections, the side effects probably outweigh the benefits.”
 

Tirzepatide, weight loss, and type 2 diabetes remission

On Sept. 21, a symposium will provide new data for the dual glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide, approved for the treatment of type 2 diabetes in the United States in May with the brand name Mounjaro. The agent is now being studied as an obesity treatment.

Data from the SURMOUNT-1 trial presented at the ADA meeting in June showed the drug produced “unprecedented” weight loss of up to 22.5%.

At EASD, those findings will be reviewed and new data presented on morbidity and mortality, along with a new commentary. The degree of weight loss seen with this new twincretin has furthered discussion about the concept of remission in type 2 diabetes, Dr. Rydén noted. That will also be the subject of the Diabetologia symposium on Sept. 21, entitled, “Remission of type 2 diabetes – fact or fiction?”

Regarding tirzepatide, Dr. Rydén said: “It’s amazing, the most powerful antiobesity drug we have at our disposal. These drugs slow gastric emptying and have other beneficial effects. … We’re now closing in on drugs that produce more than 15% weight loss. That appears to be the ‘magic bullet’ where you can achieve type 2 diabetes remission.” He pointed to a symposium sponsored by The Lancet on this topic at last year’s EASD meeting.

“I think what we want with our drugs is not to treat but actually to combat type 2 diabetes and really to achieve remission. Of course, if you’ve had it for many decades that might be impossible, but we know that particularly in the first 5-10 years it’s very important to have good glucose control and we know we can also achieve remission.”

Dr. Del Prato noted the importance of weight reduction at the time of type 2 diabetes diagnosis will be emphasized in the ADA/EASD consensus document on the management of hyperglycemia in type 2 diabetes, to be presented in its final form on Sept. 23.

“I think we’ll be learning more about potential remission in the future, both because of metabolic surgery and agents like tirzepatide. The reduction in body weight that can be achieved [with these newer drugs], or that has been reported so far, is the closest to what can be obtained with metabolic surgery. I think there will be more and more information and a lot of discussion about this, and of course about the definition of remission and what to do after remission has occurred,” Dr. Del Prato said.  

The revised ADA/EASD consensus document is expected to endorse weight loss as a “co-primary goal” of care for those without cardiorenal disease, along with early initiation of combination therapies – for example, taking two drugs immediately upon diagnosis, rather than just metformin – as opposed to the prior stepwise approach. The document will also cover use of newer glucose-lowering therapies, surgery, and behavioral interventions.  

The key is a holistic approach, Dr. Del Prato said. “Of course, glucose control is important, but it’s not the only thing. The heterogeneity of the population with diabetes is also important. Some may already have microvascular complications, kidney dysfunction, are more or less obese, and older or younger. We need to keep these differences in mind to provide more and more individualized treatment.”

Related to that, he noted, will be a joint EASD/ADA symposium on Sept. 19, entitled, “Precision medicine in type 2 diabetes: How far can we get?”
 

COVID-19 and diabetes, UKPDS, type 1 diabetes, and much more

As always, there’s a whole lot more. On Sept. 21, there will be a symposium on COVID-19 and diabetes.

Another, on diabetes technology, has a somewhat cautionary theme: “A new hope (Star Wars) or strange new worlds (Star Trek): Submerging diabetes into emerging technologies.” One of the speakers will address the question: “Are we becoming robots? Automated insulin delivery (AID) systems for everyone with type 1 diabetes: Strengths and limitations.” And this year’s EASD/JDRF symposium topic will be prevention of type 1 diabetes.

Yet another symposium on Sept. 21 will present 44-year follow-up data from the landmark United Kingdom Prospective Diabetes Study (UKPDS), including an economic analysis and a look at dementia outcomes. “It’s a historical thing. This big trial represents a gold mine of information,” Dr. Del Prato commented.

On Sept. 22, new data will be presented for the investigational once-weekly insulins during a symposium entitled, “Re-inventing the insulin experience: Exploring the prospects of once-weekly insulins.”

And lest anyone was thinking of leaving the conference early, there’s a full agenda on Sept. 23, including symposia on diabetic nephropathy, type 1 diabetes, diabetes in old age, dietary management, and the role of primary care, among others. There will also be 12 separate oral presentation sessions that day.

Overall, the meeting will reflect the multidisciplinary direction the field is headed, Dr. Rydén said.

“We’re still in an era of medicine where a lot of things happen every year. Now we have the next generation of drugs that are coming that combine many areas of treatment – obesity, cardiology, and nephrology. So, we’re integrating. The future is integrating the diabetes world with our friends in other areas of clinical medicine.”

Dr. Del Prato has reported being a consultant, advisory board member, and/or lecturer for AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Sanofi, Takeda, Eli Lilly, Abbott, and Applied Therapeutics. Dr. Rydén has reported receiving lecture fees from the Novo Nordisk Foundation and serving on advisory boards for MSD, Lilly, Boehringer Ingelheim, and AstraZeneca.

A version of this article first appeared on Medscape.com.  
 

A novel, low-dose formulation of pramipexole and rasagiline (P2B001) shows promise as a first-line treatment for patients with early-stage Parkinson’s disease. Results from a phase 3 trial found that P2B001 was superior to its components in improving motor symptoms and daily function and was comparable with marketed doses of pramipexole.

P2B001 also produced less daytime sleepiness and fewer dopaminergic effects, said the investigators, who presented findings at the International Congress of Parkinson’s Disease and Movement Disorders.

The treatment studied, P2B001, is a proprietary, fixed-dose combination of extended-release (ER) formulations of pramipexole and rasagiline. Neither dose is currently available on the market.

Investigators wanted to test the hypothesis that two anti-Parkinsonian drugs that act through different mechanisms could work synergistically, providing benefits comparable with pramipexole but with fewer side effects, said lead study author Warren Olanow, MD, professor emeritus in the neurology and neuroscience departments at the Icahn School of Medicine at Mount Sinai, New York.

Pramipexole is problematic in that it causes dopaminergic and sleep-related side effects.

Laboratory studies have shown that low doses of pramipexole and rasagiline act synergistically, said Dr. Olanow. “A previous double-blind controlled study demonstrated that P2B001 was significantly superior to placebo with respect to efficacy (P < .001) and had a good safety and tolerability profile.”
 

P2B001 outperforms other formulations

The multicenter phase 3 study (NCT03329508) enrolled 544 patients aged 35-80 with early Parkinson’s disease to assess efficacy and safety of a daily dose of P2B001, compared with its components. Patients were randomized 2:2:2:1 to 12 weeks of treatment with P2B001; pramipexole ER 0.6 mg; rasagiline ER 0.75 mg, or to a calibration arm of marketed pramipexole-ER titrated to optimal dose (mean dose, 3.2 mg).

The primary endpoint compared baseline with week 12 changes in Unified Parkinson’s Disease Rating Scale total scores for P2B001 versus its individual components. The secondary endpoint compared baseline changes in Epworth Sleepiness Scale (ESS) for P2B001 versus pramipexole-ER.

P2B001 showed superior efficacy to each of its individual components and comparable efficacy with marketed doses of pramipexole-ER. It also yielded fewer adverse events related to dopaminergic side effects and less daytime sleepiness as measured by ESS. “Further, the drug is administered once a day and does not require titration,” said Dr. Olanow.
 

Levodopa-related benefits

Another advantage of starting early-stage patients on P2B001 is that it would give patients more time to be on an effective therapy with fewer side effects before going on levodopa, the current gold standard for Parkinson’s disease treatment.

Although the American Academy of Neurology recommends levodopa as initial therapy for Parkinson’s disease, the drug has been associated with a risk of developing motor complications.

“This opinion, however, was formulated prior to the availability of the results of the P2B001 study and should be reassessed in the light of the present study,” said Dr. Olanow. Longer-term studies should assess when and if patients will require levodopa therapy, as well as the long-term effects of P2B001 on the development of motor complications in patients with early Parkinson’s disease patients.

Investigators are preparing a regulatory market approval filing for P2B001 with the Food and Drug Administration.

Dr. Olanow is CEO of Clintrex Research Corporation, which has provided services to Pharma2B, sponsor of the phase 3 study. Pharma Two B is a private, late clinical-stage pharmaceutical company in Rehovot, Israel, that owns worldwide granted patents for P2B001 pharmaceutical composition and method of treatment.

A novel, low-dose formulation of pramipexole and rasagiline (P2B001) shows promise as a first-line treatment for patients with early-stage Parkinson’s disease. Results from a phase 3 trial found that P2B001 was superior to its components in improving motor symptoms and daily function and was comparable with marketed doses of pramipexole.

P2B001 also produced less daytime sleepiness and fewer dopaminergic effects, said the investigators, who presented findings at the International Congress of Parkinson’s Disease and Movement Disorders.

The treatment studied, P2B001, is a proprietary, fixed-dose combination of extended-release (ER) formulations of pramipexole and rasagiline. Neither dose is currently available on the market.

Investigators wanted to test the hypothesis that two anti-Parkinsonian drugs that act through different mechanisms could work synergistically, providing benefits comparable with pramipexole but with fewer side effects, said lead study author Warren Olanow, MD, professor emeritus in the neurology and neuroscience departments at the Icahn School of Medicine at Mount Sinai, New York.

Pramipexole is problematic in that it causes dopaminergic and sleep-related side effects.

Laboratory studies have shown that low doses of pramipexole and rasagiline act synergistically, said Dr. Olanow. “A previous double-blind controlled study demonstrated that P2B001 was significantly superior to placebo with respect to efficacy (P < .001) and had a good safety and tolerability profile.”
 

P2B001 outperforms other formulations

The multicenter phase 3 study (NCT03329508) enrolled 544 patients aged 35-80 with early Parkinson’s disease to assess efficacy and safety of a daily dose of P2B001, compared with its components. Patients were randomized 2:2:2:1 to 12 weeks of treatment with P2B001; pramipexole ER 0.6 mg; rasagiline ER 0.75 mg, or to a calibration arm of marketed pramipexole-ER titrated to optimal dose (mean dose, 3.2 mg).

The primary endpoint compared baseline with week 12 changes in Unified Parkinson’s Disease Rating Scale total scores for P2B001 versus its individual components. The secondary endpoint compared baseline changes in Epworth Sleepiness Scale (ESS) for P2B001 versus pramipexole-ER.

P2B001 showed superior efficacy to each of its individual components and comparable efficacy with marketed doses of pramipexole-ER. It also yielded fewer adverse events related to dopaminergic side effects and less daytime sleepiness as measured by ESS. “Further, the drug is administered once a day and does not require titration,” said Dr. Olanow.
 

Levodopa-related benefits

Another advantage of starting early-stage patients on P2B001 is that it would give patients more time to be on an effective therapy with fewer side effects before going on levodopa, the current gold standard for Parkinson’s disease treatment.

Although the American Academy of Neurology recommends levodopa as initial therapy for Parkinson’s disease, the drug has been associated with a risk of developing motor complications.

“This opinion, however, was formulated prior to the availability of the results of the P2B001 study and should be reassessed in the light of the present study,” said Dr. Olanow. Longer-term studies should assess when and if patients will require levodopa therapy, as well as the long-term effects of P2B001 on the development of motor complications in patients with early Parkinson’s disease patients.

Investigators are preparing a regulatory market approval filing for P2B001 with the Food and Drug Administration.

Dr. Olanow is CEO of Clintrex Research Corporation, which has provided services to Pharma2B, sponsor of the phase 3 study. Pharma Two B is a private, late clinical-stage pharmaceutical company in Rehovot, Israel, that owns worldwide granted patents for P2B001 pharmaceutical composition and method of treatment.

A novel, low-dose formulation of pramipexole and rasagiline (P2B001) shows promise as a first-line treatment for patients with early-stage Parkinson’s disease. Results from a phase 3 trial found that P2B001 was superior to its components in improving motor symptoms and daily function and was comparable with marketed doses of pramipexole.

P2B001 also produced less daytime sleepiness and fewer dopaminergic effects, said the investigators, who presented findings at the International Congress of Parkinson’s Disease and Movement Disorders.

The treatment studied, P2B001, is a proprietary, fixed-dose combination of extended-release (ER) formulations of pramipexole and rasagiline. Neither dose is currently available on the market.

Investigators wanted to test the hypothesis that two anti-Parkinsonian drugs that act through different mechanisms could work synergistically, providing benefits comparable with pramipexole but with fewer side effects, said lead study author Warren Olanow, MD, professor emeritus in the neurology and neuroscience departments at the Icahn School of Medicine at Mount Sinai, New York.

Pramipexole is problematic in that it causes dopaminergic and sleep-related side effects.

Laboratory studies have shown that low doses of pramipexole and rasagiline act synergistically, said Dr. Olanow. “A previous double-blind controlled study demonstrated that P2B001 was significantly superior to placebo with respect to efficacy (P < .001) and had a good safety and tolerability profile.”
 

P2B001 outperforms other formulations

The multicenter phase 3 study (NCT03329508) enrolled 544 patients aged 35-80 with early Parkinson’s disease to assess efficacy and safety of a daily dose of P2B001, compared with its components. Patients were randomized 2:2:2:1 to 12 weeks of treatment with P2B001; pramipexole ER 0.6 mg; rasagiline ER 0.75 mg, or to a calibration arm of marketed pramipexole-ER titrated to optimal dose (mean dose, 3.2 mg).

The primary endpoint compared baseline with week 12 changes in Unified Parkinson’s Disease Rating Scale total scores for P2B001 versus its individual components. The secondary endpoint compared baseline changes in Epworth Sleepiness Scale (ESS) for P2B001 versus pramipexole-ER.

P2B001 showed superior efficacy to each of its individual components and comparable efficacy with marketed doses of pramipexole-ER. It also yielded fewer adverse events related to dopaminergic side effects and less daytime sleepiness as measured by ESS. “Further, the drug is administered once a day and does not require titration,” said Dr. Olanow.
 

Levodopa-related benefits

Another advantage of starting early-stage patients on P2B001 is that it would give patients more time to be on an effective therapy with fewer side effects before going on levodopa, the current gold standard for Parkinson’s disease treatment.

Although the American Academy of Neurology recommends levodopa as initial therapy for Parkinson’s disease, the drug has been associated with a risk of developing motor complications.

“This opinion, however, was formulated prior to the availability of the results of the P2B001 study and should be reassessed in the light of the present study,” said Dr. Olanow. Longer-term studies should assess when and if patients will require levodopa therapy, as well as the long-term effects of P2B001 on the development of motor complications in patients with early Parkinson’s disease patients.

Investigators are preparing a regulatory market approval filing for P2B001 with the Food and Drug Administration.

Dr. Olanow is CEO of Clintrex Research Corporation, which has provided services to Pharma2B, sponsor of the phase 3 study. Pharma Two B is a private, late clinical-stage pharmaceutical company in Rehovot, Israel, that owns worldwide granted patents for P2B001 pharmaceutical composition and method of treatment.

PORTLAND, ORE. – Some pernio-like/chilblains-like lesions on the toes – which became widely known as “COVID toes” – and other acral sites that have occurred during the COVID-19 pandemic are related to COVID-19 infection, while others are not, according to Lindy P. Fox, MD, professor of dermatology and director of the hospital consultation service at the University of California, San Francisco.

“We’re learning a lot about pernio because of COVID,” Dr. Fox, a member of the American Academy of Dermatology’s Ad Hoc Task Force on COVID-19, said at the annual meeting of the Pacific Dermatologic Association. “Patients with pernio tend to either have bright red or purple individual lesions or an erythromelalgia-like presentation, often waking up in the middle of the night saying ‘my feet hurt. I can’t put sheets over my feet.’ In my experience, the patients with an erythromelalgia-like presentation tend to be a lot harder to treat.”

courtesy UCSF

Establishing terminology to describe pernio-like lesions was a challenge in the early stages of the COVID-19 pandemic, Dr. Fox added, with clinicians using terms like erythema multiforme-like, coxsackie-like, or even necrotic to describe the lesions. “I don’t think pernio is truly necrotic; I think it’s really inflammatory and purpuric,” she said.

Early in the pandemic, studies suggesting a link with these cases and COVID-19 infection include a case series of 318 patients with pernio-like skin lesions who had confirmed or suspected COVID-19. Most of these patients were generally young and healthy and most had relatively mild COVID-19; 7% were laboratory-confirmed COVID-19 positive, and 6% were close contacts of patients with confirmed COVID-19. Pernio-like lesions were the only symptoms in 55% of the patients.

In another study, researchers in France evaluated the clinical, laboratory, and pathologic characteristics of 40 patients who developed chilblain-like lesions (mostly involving the toes) during the COVID-19 pandemic and were seen as outpatients in April 2020 . All were polymerase chain reaction (PCR) negative, 30% were SARS-CoV-2 serology positive, and 60% had elevated D-dimers. Histology obtained from 19 of the patients revealed lymphocytic inflammation and vascular damage, and 8 had IgA positivity.

In a retrospective analysis of seven pediatric chilblains cases during the pandemic, researchers examined the skin biopsies to evaluate histopathological features and explored the presence of SARS-CoV-2 in the tissue. All patients were PCR negative. The authors observed cytoplasmic granular positivity for SARS-CoV-2 spike protein in endothelial cells, a feature that they said showed coronavirus-like particles, consistent with SARS-CoV-2.

Not all studies in the medical literature have demonstrated an association between pernio-like/chilblains-like lesions and COVID-19, though. An analysis of 23 patients, with skin eruptions considered associated with SARS-CoV-2 infections (including 21 cases of chilblains) during the first wave of the pandemic found that the antibody and T-cell response in patients with pandemic chilblains was the same as in negative controls.

“What’s remarkably interesting about this study is that they did autopsies of samples from patients who had died prepandemic, so there was no such thing as COVID-19,” said Dr. Fox, who was not involved with the study. “They stained for viral particles in those patients, and they were positive in a subset of patients. This makes me wonder about what the significance of that staining positivity is.”

Yet another group of investigators looked at what was happening with pernio during the waves of COVID in a study of chilblains cases in children in Spain, and found a stronger association between lockdown and cold temperature, which argues against a direct association between pernio and COVID infection.

In Dr. Fox’s experience, COVID toes can recur, especially upon exposure to cold. “What taught me this in real life is a patient who I saw remotely by video,” she recalled. “It was early on in the pandemic. I could not prove he had COVID no matter how hard I tried, but I do think he had COVID toes at that time.” When he later was confirmed to have COVID, “he got pernio in the same exact location as his original suspected COVID toes.”

According to an analysis of long COVID in the skin, based on cases reported to the American Academy of Dermatology–International League of Dermatological Societies registry from April 8 to Oct. 8, 2020, pernio-like lesions lasted a median of 12 days in patients with lab-confirmed COVID-19 and a median of 15 days in those with suspected COVID-19. But almost 7% of the 103 pernio cases were long-haulers, defined as those with dermatologic signs of COVID that lasted beyond 60 days.

“There are some patients who are resistant to treatment,” Dr. Fox said. “In addition, recurrent lesions make me think that maybe all pernio is triggered by some viral cause. This causes an immunologic phenomenon that’s responding to a viral trigger you’re trying to deal with. That may be the better way to think about COVID toes.”

Different variants of COVID also appear to be changing the characteristics of dermatologic manifestations associated with infection. Results from a large retrospective analysis of nearly 350,000 users of a COVID study App in the United Kingdom found that skin lesions were more predictive of a positive test in the Delta wave, compared with the Omicron wave, while pernio-like lesions were predictive of infection in the Delta wave but not in the Omicron wave.

“And, whether you were vaccinated or unvaccinated really did not influence whether or not you were going to have a skin rash as a presenting sign of COVID, except for the burning rash, which was less in vaccinated patients,” said Dr. Fox, who was not involved with the study.

Dr. Fox reported having no relevant disclosures.

PORTLAND, ORE. – Some pernio-like/chilblains-like lesions on the toes – which became widely known as “COVID toes” – and other acral sites that have occurred during the COVID-19 pandemic are related to COVID-19 infection, while others are not, according to Lindy P. Fox, MD, professor of dermatology and director of the hospital consultation service at the University of California, San Francisco.

“We’re learning a lot about pernio because of COVID,” Dr. Fox, a member of the American Academy of Dermatology’s Ad Hoc Task Force on COVID-19, said at the annual meeting of the Pacific Dermatologic Association. “Patients with pernio tend to either have bright red or purple individual lesions or an erythromelalgia-like presentation, often waking up in the middle of the night saying ‘my feet hurt. I can’t put sheets over my feet.’ In my experience, the patients with an erythromelalgia-like presentation tend to be a lot harder to treat.”

courtesy UCSF

Establishing terminology to describe pernio-like lesions was a challenge in the early stages of the COVID-19 pandemic, Dr. Fox added, with clinicians using terms like erythema multiforme-like, coxsackie-like, or even necrotic to describe the lesions. “I don’t think pernio is truly necrotic; I think it’s really inflammatory and purpuric,” she said.

Early in the pandemic, studies suggesting a link with these cases and COVID-19 infection include a case series of 318 patients with pernio-like skin lesions who had confirmed or suspected COVID-19. Most of these patients were generally young and healthy and most had relatively mild COVID-19; 7% were laboratory-confirmed COVID-19 positive, and 6% were close contacts of patients with confirmed COVID-19. Pernio-like lesions were the only symptoms in 55% of the patients.

In another study, researchers in France evaluated the clinical, laboratory, and pathologic characteristics of 40 patients who developed chilblain-like lesions (mostly involving the toes) during the COVID-19 pandemic and were seen as outpatients in April 2020 . All were polymerase chain reaction (PCR) negative, 30% were SARS-CoV-2 serology positive, and 60% had elevated D-dimers. Histology obtained from 19 of the patients revealed lymphocytic inflammation and vascular damage, and 8 had IgA positivity.

In a retrospective analysis of seven pediatric chilblains cases during the pandemic, researchers examined the skin biopsies to evaluate histopathological features and explored the presence of SARS-CoV-2 in the tissue. All patients were PCR negative. The authors observed cytoplasmic granular positivity for SARS-CoV-2 spike protein in endothelial cells, a feature that they said showed coronavirus-like particles, consistent with SARS-CoV-2.

Not all studies in the medical literature have demonstrated an association between pernio-like/chilblains-like lesions and COVID-19, though. An analysis of 23 patients, with skin eruptions considered associated with SARS-CoV-2 infections (including 21 cases of chilblains) during the first wave of the pandemic found that the antibody and T-cell response in patients with pandemic chilblains was the same as in negative controls.

“What’s remarkably interesting about this study is that they did autopsies of samples from patients who had died prepandemic, so there was no such thing as COVID-19,” said Dr. Fox, who was not involved with the study. “They stained for viral particles in those patients, and they were positive in a subset of patients. This makes me wonder about what the significance of that staining positivity is.”

Yet another group of investigators looked at what was happening with pernio during the waves of COVID in a study of chilblains cases in children in Spain, and found a stronger association between lockdown and cold temperature, which argues against a direct association between pernio and COVID infection.

In Dr. Fox’s experience, COVID toes can recur, especially upon exposure to cold. “What taught me this in real life is a patient who I saw remotely by video,” she recalled. “It was early on in the pandemic. I could not prove he had COVID no matter how hard I tried, but I do think he had COVID toes at that time.” When he later was confirmed to have COVID, “he got pernio in the same exact location as his original suspected COVID toes.”

According to an analysis of long COVID in the skin, based on cases reported to the American Academy of Dermatology–International League of Dermatological Societies registry from April 8 to Oct. 8, 2020, pernio-like lesions lasted a median of 12 days in patients with lab-confirmed COVID-19 and a median of 15 days in those with suspected COVID-19. But almost 7% of the 103 pernio cases were long-haulers, defined as those with dermatologic signs of COVID that lasted beyond 60 days.

“There are some patients who are resistant to treatment,” Dr. Fox said. “In addition, recurrent lesions make me think that maybe all pernio is triggered by some viral cause. This causes an immunologic phenomenon that’s responding to a viral trigger you’re trying to deal with. That may be the better way to think about COVID toes.”

Different variants of COVID also appear to be changing the characteristics of dermatologic manifestations associated with infection. Results from a large retrospective analysis of nearly 350,000 users of a COVID study App in the United Kingdom found that skin lesions were more predictive of a positive test in the Delta wave, compared with the Omicron wave, while pernio-like lesions were predictive of infection in the Delta wave but not in the Omicron wave.

“And, whether you were vaccinated or unvaccinated really did not influence whether or not you were going to have a skin rash as a presenting sign of COVID, except for the burning rash, which was less in vaccinated patients,” said Dr. Fox, who was not involved with the study.

Dr. Fox reported having no relevant disclosures.

PORTLAND, ORE. – Some pernio-like/chilblains-like lesions on the toes – which became widely known as “COVID toes” – and other acral sites that have occurred during the COVID-19 pandemic are related to COVID-19 infection, while others are not, according to Lindy P. Fox, MD, professor of dermatology and director of the hospital consultation service at the University of California, San Francisco.

“We’re learning a lot about pernio because of COVID,” Dr. Fox, a member of the American Academy of Dermatology’s Ad Hoc Task Force on COVID-19, said at the annual meeting of the Pacific Dermatologic Association. “Patients with pernio tend to either have bright red or purple individual lesions or an erythromelalgia-like presentation, often waking up in the middle of the night saying ‘my feet hurt. I can’t put sheets over my feet.’ In my experience, the patients with an erythromelalgia-like presentation tend to be a lot harder to treat.”

courtesy UCSF

Establishing terminology to describe pernio-like lesions was a challenge in the early stages of the COVID-19 pandemic, Dr. Fox added, with clinicians using terms like erythema multiforme-like, coxsackie-like, or even necrotic to describe the lesions. “I don’t think pernio is truly necrotic; I think it’s really inflammatory and purpuric,” she said.

Early in the pandemic, studies suggesting a link with these cases and COVID-19 infection include a case series of 318 patients with pernio-like skin lesions who had confirmed or suspected COVID-19. Most of these patients were generally young and healthy and most had relatively mild COVID-19; 7% were laboratory-confirmed COVID-19 positive, and 6% were close contacts of patients with confirmed COVID-19. Pernio-like lesions were the only symptoms in 55% of the patients.

In another study, researchers in France evaluated the clinical, laboratory, and pathologic characteristics of 40 patients who developed chilblain-like lesions (mostly involving the toes) during the COVID-19 pandemic and were seen as outpatients in April 2020 . All were polymerase chain reaction (PCR) negative, 30% were SARS-CoV-2 serology positive, and 60% had elevated D-dimers. Histology obtained from 19 of the patients revealed lymphocytic inflammation and vascular damage, and 8 had IgA positivity.

In a retrospective analysis of seven pediatric chilblains cases during the pandemic, researchers examined the skin biopsies to evaluate histopathological features and explored the presence of SARS-CoV-2 in the tissue. All patients were PCR negative. The authors observed cytoplasmic granular positivity for SARS-CoV-2 spike protein in endothelial cells, a feature that they said showed coronavirus-like particles, consistent with SARS-CoV-2.

Not all studies in the medical literature have demonstrated an association between pernio-like/chilblains-like lesions and COVID-19, though. An analysis of 23 patients, with skin eruptions considered associated with SARS-CoV-2 infections (including 21 cases of chilblains) during the first wave of the pandemic found that the antibody and T-cell response in patients with pandemic chilblains was the same as in negative controls.

“What’s remarkably interesting about this study is that they did autopsies of samples from patients who had died prepandemic, so there was no such thing as COVID-19,” said Dr. Fox, who was not involved with the study. “They stained for viral particles in those patients, and they were positive in a subset of patients. This makes me wonder about what the significance of that staining positivity is.”

Yet another group of investigators looked at what was happening with pernio during the waves of COVID in a study of chilblains cases in children in Spain, and found a stronger association between lockdown and cold temperature, which argues against a direct association between pernio and COVID infection.

In Dr. Fox’s experience, COVID toes can recur, especially upon exposure to cold. “What taught me this in real life is a patient who I saw remotely by video,” she recalled. “It was early on in the pandemic. I could not prove he had COVID no matter how hard I tried, but I do think he had COVID toes at that time.” When he later was confirmed to have COVID, “he got pernio in the same exact location as his original suspected COVID toes.”

According to an analysis of long COVID in the skin, based on cases reported to the American Academy of Dermatology–International League of Dermatological Societies registry from April 8 to Oct. 8, 2020, pernio-like lesions lasted a median of 12 days in patients with lab-confirmed COVID-19 and a median of 15 days in those with suspected COVID-19. But almost 7% of the 103 pernio cases were long-haulers, defined as those with dermatologic signs of COVID that lasted beyond 60 days.

“There are some patients who are resistant to treatment,” Dr. Fox said. “In addition, recurrent lesions make me think that maybe all pernio is triggered by some viral cause. This causes an immunologic phenomenon that’s responding to a viral trigger you’re trying to deal with. That may be the better way to think about COVID toes.”

Different variants of COVID also appear to be changing the characteristics of dermatologic manifestations associated with infection. Results from a large retrospective analysis of nearly 350,000 users of a COVID study App in the United Kingdom found that skin lesions were more predictive of a positive test in the Delta wave, compared with the Omicron wave, while pernio-like lesions were predictive of infection in the Delta wave but not in the Omicron wave.

“And, whether you were vaccinated or unvaccinated really did not influence whether or not you were going to have a skin rash as a presenting sign of COVID, except for the burning rash, which was less in vaccinated patients,” said Dr. Fox, who was not involved with the study.

Dr. Fox reported having no relevant disclosures.

SAN DIEGO – The US Department of Veterans Affairs (VA) TeleOncology program has rolled out a virtual tumor board that brings medical professionals together to offer insight and guidance about challenging hematology cases. Over the past 6 months the board has held 10 sessions and reviewed about 20 cases. A small survey found that participants think the meetings are beneficial. 

“Virtual tumor boards help to connect experts across the country to leverage the expertise within the VA,” he-matologist/oncologist Thomas Rodgers, MD, of the Duke Cancer Institute and Durham Veterans Affairs Medical Center, told Federal Practitioner in an interview. He is the lead author of a poster about the program that was pre-sented here at the annual meeting of the Association of VA Hematology/Oncology (AVAHO).

As Dr. Rodgers noted, tumor boards are already in place at some VA centers. However, “they are not available at every VA and often are not set up to cover every cancer type.”

The VA National TeleOncology program created the virtual tumor board program as part of its mission to ex-tend hematology/oncology services across the system. “Cancer care has become increasingly complex. Beyond ad-vancing therapeutics, patient care often involves multiple specialties and medical disciplines,” Dr. Rodgers said. “A tumor board offers a forum for these specialists to communicate with each other in real time, not only to help estab-lish the correct diagnosis and stage of cancer but also to form a consensus on the most fitting treatment option. Think of it as getting all of the people involved in a person’s care in the same room.”

Currently, he said, the virtual tumor boards cover patients with malignant hematology diagnoses such as leuke-mia, multiple myeloma, and lymphomas. “We welcome submissions. If a provider is interested in submitting a case, they can email us and will be provided with a short intake form. Once submitted, we will collect necessary imaging and pathology for review. The provider will then present the patient case on the day of the tumor board.”

Typically, more than 30 medical professionals participate in the virtual tumor boards, Dr. Rodgers said, repre-senting medical oncology/hematology, pathology, radiology, palliative care, pharmacy, social work, and die-tary/nutrition. 

According to the poster presented at AVAHO, 9 participants responded to a survey after 4 tumor board sessions. All found the boards to be beneficial or somewhat beneficial, and 55% reported that they were “highly applicable” to their practice. 

Pathologist Claudio A. Mosse, MD, PhD, of Vanderbilt University Medical Center and VA Tennessee Valley Healthcare System, praised the virtual tumor board program. “It’s been incredibly useful from my end as a pathologist as it shows me which diagnoses are most challenging for my colleagues,” Dr. Mosse said in an inter-view. “Reviewing and then presenting these challenging cases forces me to go into the published literature to come to a unitary diagnosis based on the patient history, radiology, various laboratory tests, and the biopsy I was asked to review.”

He added that “as a pathologist, I learn so much from the hematologists as they discuss the possible therapeutic options, and that strengthens my ability as a pathologist because I have to understand how one diagnosis versus an-other affects their therapeutic decision tree.”

What’s next for the virtual tumor board program? The next step is to expand to solid tumors, said VA Pittsburgh Healthcare System hematologist/oncologist Vida Almario Passero, MD, MBA, chief medical officer of National TeleOncology, in an interview. 

No disclosures were reported.

SAN DIEGO – The US Department of Veterans Affairs (VA) TeleOncology program has rolled out a virtual tumor board that brings medical professionals together to offer insight and guidance about challenging hematology cases. Over the past 6 months the board has held 10 sessions and reviewed about 20 cases. A small survey found that participants think the meetings are beneficial. 

“Virtual tumor boards help to connect experts across the country to leverage the expertise within the VA,” he-matologist/oncologist Thomas Rodgers, MD, of the Duke Cancer Institute and Durham Veterans Affairs Medical Center, told Federal Practitioner in an interview. He is the lead author of a poster about the program that was pre-sented here at the annual meeting of the Association of VA Hematology/Oncology (AVAHO).

As Dr. Rodgers noted, tumor boards are already in place at some VA centers. However, “they are not available at every VA and often are not set up to cover every cancer type.”

The VA National TeleOncology program created the virtual tumor board program as part of its mission to ex-tend hematology/oncology services across the system. “Cancer care has become increasingly complex. Beyond ad-vancing therapeutics, patient care often involves multiple specialties and medical disciplines,” Dr. Rodgers said. “A tumor board offers a forum for these specialists to communicate with each other in real time, not only to help estab-lish the correct diagnosis and stage of cancer but also to form a consensus on the most fitting treatment option. Think of it as getting all of the people involved in a person’s care in the same room.”

Currently, he said, the virtual tumor boards cover patients with malignant hematology diagnoses such as leuke-mia, multiple myeloma, and lymphomas. “We welcome submissions. If a provider is interested in submitting a case, they can email us and will be provided with a short intake form. Once submitted, we will collect necessary imaging and pathology for review. The provider will then present the patient case on the day of the tumor board.”

Typically, more than 30 medical professionals participate in the virtual tumor boards, Dr. Rodgers said, repre-senting medical oncology/hematology, pathology, radiology, palliative care, pharmacy, social work, and die-tary/nutrition. 

According to the poster presented at AVAHO, 9 participants responded to a survey after 4 tumor board sessions. All found the boards to be beneficial or somewhat beneficial, and 55% reported that they were “highly applicable” to their practice. 

Pathologist Claudio A. Mosse, MD, PhD, of Vanderbilt University Medical Center and VA Tennessee Valley Healthcare System, praised the virtual tumor board program. “It’s been incredibly useful from my end as a pathologist as it shows me which diagnoses are most challenging for my colleagues,” Dr. Mosse said in an inter-view. “Reviewing and then presenting these challenging cases forces me to go into the published literature to come to a unitary diagnosis based on the patient history, radiology, various laboratory tests, and the biopsy I was asked to review.”

He added that “as a pathologist, I learn so much from the hematologists as they discuss the possible therapeutic options, and that strengthens my ability as a pathologist because I have to understand how one diagnosis versus an-other affects their therapeutic decision tree.”

What’s next for the virtual tumor board program? The next step is to expand to solid tumors, said VA Pittsburgh Healthcare System hematologist/oncologist Vida Almario Passero, MD, MBA, chief medical officer of National TeleOncology, in an interview. 

No disclosures were reported.

SAN DIEGO – The US Department of Veterans Affairs (VA) TeleOncology program has rolled out a virtual tumor board that brings medical professionals together to offer insight and guidance about challenging hematology cases. Over the past 6 months the board has held 10 sessions and reviewed about 20 cases. A small survey found that participants think the meetings are beneficial. 

“Virtual tumor boards help to connect experts across the country to leverage the expertise within the VA,” he-matologist/oncologist Thomas Rodgers, MD, of the Duke Cancer Institute and Durham Veterans Affairs Medical Center, told Federal Practitioner in an interview. He is the lead author of a poster about the program that was pre-sented here at the annual meeting of the Association of VA Hematology/Oncology (AVAHO).

As Dr. Rodgers noted, tumor boards are already in place at some VA centers. However, “they are not available at every VA and often are not set up to cover every cancer type.”

The VA National TeleOncology program created the virtual tumor board program as part of its mission to ex-tend hematology/oncology services across the system. “Cancer care has become increasingly complex. Beyond ad-vancing therapeutics, patient care often involves multiple specialties and medical disciplines,” Dr. Rodgers said. “A tumor board offers a forum for these specialists to communicate with each other in real time, not only to help estab-lish the correct diagnosis and stage of cancer but also to form a consensus on the most fitting treatment option. Think of it as getting all of the people involved in a person’s care in the same room.”

Currently, he said, the virtual tumor boards cover patients with malignant hematology diagnoses such as leuke-mia, multiple myeloma, and lymphomas. “We welcome submissions. If a provider is interested in submitting a case, they can email us and will be provided with a short intake form. Once submitted, we will collect necessary imaging and pathology for review. The provider will then present the patient case on the day of the tumor board.”

Typically, more than 30 medical professionals participate in the virtual tumor boards, Dr. Rodgers said, repre-senting medical oncology/hematology, pathology, radiology, palliative care, pharmacy, social work, and die-tary/nutrition. 

According to the poster presented at AVAHO, 9 participants responded to a survey after 4 tumor board sessions. All found the boards to be beneficial or somewhat beneficial, and 55% reported that they were “highly applicable” to their practice. 

Pathologist Claudio A. Mosse, MD, PhD, of Vanderbilt University Medical Center and VA Tennessee Valley Healthcare System, praised the virtual tumor board program. “It’s been incredibly useful from my end as a pathologist as it shows me which diagnoses are most challenging for my colleagues,” Dr. Mosse said in an inter-view. “Reviewing and then presenting these challenging cases forces me to go into the published literature to come to a unitary diagnosis based on the patient history, radiology, various laboratory tests, and the biopsy I was asked to review.”

He added that “as a pathologist, I learn so much from the hematologists as they discuss the possible therapeutic options, and that strengthens my ability as a pathologist because I have to understand how one diagnosis versus an-other affects their therapeutic decision tree.”

What’s next for the virtual tumor board program? The next step is to expand to solid tumors, said VA Pittsburgh Healthcare System hematologist/oncologist Vida Almario Passero, MD, MBA, chief medical officer of National TeleOncology, in an interview. 

No disclosures were reported.

Time to diagnosis is a crucial factor in cancer. Delays can lead to diagnosis at later stages and prevent optimal therapeutic strategies, both of which have the potential to reduce survival. An estimated 63%-82% of cancers get diagnosed as a result of symptom presentation, and delays in diagnosis can hamper treatment efforts. Diagnosis can be challenging because common symptoms – such as weight loss, weakness, poor appetite, and shortness of breath – are nonspecific.

A new analysis of U.S.-based data shows that the average time to diagnosis is 5.2 months for patients with solid tumors. The authors of the study call for better cancer diagnosis pathways in the U.S.

“Several countries, including the UK, Denmark, Sweden, Canada and Australia, have identified the importance and potential impact of more timely diagnosis by establishing national guidelines, special programs, and treatment pathways. However, in the U.S., there’s relatively little research and effort focused on streamlining the diagnostic pathway. Currently, the U.S. does not have established cancer diagnostic pathways that are used consistently,” Matthew Gitlin, PharmD, said during a presentation at the annual meeting of the European Society for Medical Oncology.

Diagnostic delays can lead to diagnosis at more advanced stages. “That is often associated with worse clinical outcomes, increased economic burden, and decreased health related quality of life,” said Dr. Gitlin, founder and managing director of the health economics consulting firm BluePath Solutions, which conducted the analysis.

The study retrospectively examined administrative billing data drawn from the Clinformatics for Managed Markets longitudinal database. The data represent individuals in Medicare Advantage and a large, U.S.-based private insurance plan. Between 2018 and 2019, there were 458,818 cancer diagnoses. The mean age was 70.6 years and 49.6% of the patients were female. Sixty-five percent were White, 11.1% Black, 8.3% Hispanic, and 2.5% Asian. No race data were available for 13.2%. Medicare Advantage was the primary insurance carrier for 74.0%, and 24.0% had a commercial plan.

The mean time to diagnosis across all tumors was 5.2 months (standard deviation, 5.5 months). There was significant variation across different tumor types, as well as within the same tumor type. The median value was 3.9 months (interquartile range, 1.1-7.2 months).

Mean time to diagnosis ranged from 121.6 days for bladder cancer to as high as 229 days for multiple myeloma. Standard deviations were nearly as large or even larger than the mean values. The study showed that 15.8% of patients waited 6 months or longer for a diagnosis. Delays were most common in kidney cancer, colorectal cancer, gallbladder cancer, esophageal cancer, stomach cancer, lymphoma, and multiple myeloma: More than 25% of patients had a time to diagnosis of at least 6 months in these tumors.

“Although there is limited research in the published literature, our findings are consistent with that literature that does exist. Development or modification of policies, guidelines or medical interventions that streamline the diagnostic pathway are needed to optimize patient outcomes and reduce resource burden and cost to the health care system,” Dr. Gitlin said.

Previous literature on this topic has seen wide variation in how time to diagnosis is defined, and most research is conducted in high-income countries, according to Felipe Roitberg, PhD, who served as a discussant during the session. “Most of the countries and patients in need are localized in low- and middle-income countries, so that is a call to action (for more research),” said Dr. Roitberg, a clinical oncologist at Hospital Sírio Libanês in São Paulo, Brazil.

The study did not look at the associations between race and time to diagnosis. “This is a source of analysis could further be explored,” said Dr. Roitberg.

He noted that the ABC-DO prospective cohort study in sub-Saharan Africa found large variations in breast cancer survival by country, and its authors predicted that downstaging and improvements in treatment could prevent up to one-third of projected breast cancer deaths over the next decade. “So these are the drivers of populational gain in terms of overall survival – not more drugs, not more services available, but coordination of services and making sure the patient has a right pathway (to diagnosis and treatment),” Dr. Roitberg said.

Dr. Gitlin has received consulting fees from GRAIL LLC, which is a subsidiary of Illumina. Dr. Roitberg has received honoraria from Boehringer Ingelheim, Sanofi, Roche, MSD Oncology, AstraZeneca, Nestle Health Science, Dr Reddy’s, and Oncologia Brazil. He has consulted for MSD Oncology. He has received research funding from Roche, Boehringer Ingelheim, MSD, Bayer, AstraZeneca, and Takeda.

Time to diagnosis is a crucial factor in cancer. Delays can lead to diagnosis at later stages and prevent optimal therapeutic strategies, both of which have the potential to reduce survival. An estimated 63%-82% of cancers get diagnosed as a result of symptom presentation, and delays in diagnosis can hamper treatment efforts. Diagnosis can be challenging because common symptoms – such as weight loss, weakness, poor appetite, and shortness of breath – are nonspecific.

A new analysis of U.S.-based data shows that the average time to diagnosis is 5.2 months for patients with solid tumors. The authors of the study call for better cancer diagnosis pathways in the U.S.

“Several countries, including the UK, Denmark, Sweden, Canada and Australia, have identified the importance and potential impact of more timely diagnosis by establishing national guidelines, special programs, and treatment pathways. However, in the U.S., there’s relatively little research and effort focused on streamlining the diagnostic pathway. Currently, the U.S. does not have established cancer diagnostic pathways that are used consistently,” Matthew Gitlin, PharmD, said during a presentation at the annual meeting of the European Society for Medical Oncology.

Diagnostic delays can lead to diagnosis at more advanced stages. “That is often associated with worse clinical outcomes, increased economic burden, and decreased health related quality of life,” said Dr. Gitlin, founder and managing director of the health economics consulting firm BluePath Solutions, which conducted the analysis.

The study retrospectively examined administrative billing data drawn from the Clinformatics for Managed Markets longitudinal database. The data represent individuals in Medicare Advantage and a large, U.S.-based private insurance plan. Between 2018 and 2019, there were 458,818 cancer diagnoses. The mean age was 70.6 years and 49.6% of the patients were female. Sixty-five percent were White, 11.1% Black, 8.3% Hispanic, and 2.5% Asian. No race data were available for 13.2%. Medicare Advantage was the primary insurance carrier for 74.0%, and 24.0% had a commercial plan.

The mean time to diagnosis across all tumors was 5.2 months (standard deviation, 5.5 months). There was significant variation across different tumor types, as well as within the same tumor type. The median value was 3.9 months (interquartile range, 1.1-7.2 months).

Mean time to diagnosis ranged from 121.6 days for bladder cancer to as high as 229 days for multiple myeloma. Standard deviations were nearly as large or even larger than the mean values. The study showed that 15.8% of patients waited 6 months or longer for a diagnosis. Delays were most common in kidney cancer, colorectal cancer, gallbladder cancer, esophageal cancer, stomach cancer, lymphoma, and multiple myeloma: More than 25% of patients had a time to diagnosis of at least 6 months in these tumors.

“Although there is limited research in the published literature, our findings are consistent with that literature that does exist. Development or modification of policies, guidelines or medical interventions that streamline the diagnostic pathway are needed to optimize patient outcomes and reduce resource burden and cost to the health care system,” Dr. Gitlin said.

Previous literature on this topic has seen wide variation in how time to diagnosis is defined, and most research is conducted in high-income countries, according to Felipe Roitberg, PhD, who served as a discussant during the session. “Most of the countries and patients in need are localized in low- and middle-income countries, so that is a call to action (for more research),” said Dr. Roitberg, a clinical oncologist at Hospital Sírio Libanês in São Paulo, Brazil.

The study did not look at the associations between race and time to diagnosis. “This is a source of analysis could further be explored,” said Dr. Roitberg.

He noted that the ABC-DO prospective cohort study in sub-Saharan Africa found large variations in breast cancer survival by country, and its authors predicted that downstaging and improvements in treatment could prevent up to one-third of projected breast cancer deaths over the next decade. “So these are the drivers of populational gain in terms of overall survival – not more drugs, not more services available, but coordination of services and making sure the patient has a right pathway (to diagnosis and treatment),” Dr. Roitberg said.

Dr. Gitlin has received consulting fees from GRAIL LLC, which is a subsidiary of Illumina. Dr. Roitberg has received honoraria from Boehringer Ingelheim, Sanofi, Roche, MSD Oncology, AstraZeneca, Nestle Health Science, Dr Reddy’s, and Oncologia Brazil. He has consulted for MSD Oncology. He has received research funding from Roche, Boehringer Ingelheim, MSD, Bayer, AstraZeneca, and Takeda.

Time to diagnosis is a crucial factor in cancer. Delays can lead to diagnosis at later stages and prevent optimal therapeutic strategies, both of which have the potential to reduce survival. An estimated 63%-82% of cancers get diagnosed as a result of symptom presentation, and delays in diagnosis can hamper treatment efforts. Diagnosis can be challenging because common symptoms – such as weight loss, weakness, poor appetite, and shortness of breath – are nonspecific.

A new analysis of U.S.-based data shows that the average time to diagnosis is 5.2 months for patients with solid tumors. The authors of the study call for better cancer diagnosis pathways in the U.S.

“Several countries, including the UK, Denmark, Sweden, Canada and Australia, have identified the importance and potential impact of more timely diagnosis by establishing national guidelines, special programs, and treatment pathways. However, in the U.S., there’s relatively little research and effort focused on streamlining the diagnostic pathway. Currently, the U.S. does not have established cancer diagnostic pathways that are used consistently,” Matthew Gitlin, PharmD, said during a presentation at the annual meeting of the European Society for Medical Oncology.

Diagnostic delays can lead to diagnosis at more advanced stages. “That is often associated with worse clinical outcomes, increased economic burden, and decreased health related quality of life,” said Dr. Gitlin, founder and managing director of the health economics consulting firm BluePath Solutions, which conducted the analysis.

The study retrospectively examined administrative billing data drawn from the Clinformatics for Managed Markets longitudinal database. The data represent individuals in Medicare Advantage and a large, U.S.-based private insurance plan. Between 2018 and 2019, there were 458,818 cancer diagnoses. The mean age was 70.6 years and 49.6% of the patients were female. Sixty-five percent were White, 11.1% Black, 8.3% Hispanic, and 2.5% Asian. No race data were available for 13.2%. Medicare Advantage was the primary insurance carrier for 74.0%, and 24.0% had a commercial plan.

The mean time to diagnosis across all tumors was 5.2 months (standard deviation, 5.5 months). There was significant variation across different tumor types, as well as within the same tumor type. The median value was 3.9 months (interquartile range, 1.1-7.2 months).

Mean time to diagnosis ranged from 121.6 days for bladder cancer to as high as 229 days for multiple myeloma. Standard deviations were nearly as large or even larger than the mean values. The study showed that 15.8% of patients waited 6 months or longer for a diagnosis. Delays were most common in kidney cancer, colorectal cancer, gallbladder cancer, esophageal cancer, stomach cancer, lymphoma, and multiple myeloma: More than 25% of patients had a time to diagnosis of at least 6 months in these tumors.

“Although there is limited research in the published literature, our findings are consistent with that literature that does exist. Development or modification of policies, guidelines or medical interventions that streamline the diagnostic pathway are needed to optimize patient outcomes and reduce resource burden and cost to the health care system,” Dr. Gitlin said.

Previous literature on this topic has seen wide variation in how time to diagnosis is defined, and most research is conducted in high-income countries, according to Felipe Roitberg, PhD, who served as a discussant during the session. “Most of the countries and patients in need are localized in low- and middle-income countries, so that is a call to action (for more research),” said Dr. Roitberg, a clinical oncologist at Hospital Sírio Libanês in São Paulo, Brazil.

The study did not look at the associations between race and time to diagnosis. “This is a source of analysis could further be explored,” said Dr. Roitberg.

He noted that the ABC-DO prospective cohort study in sub-Saharan Africa found large variations in breast cancer survival by country, and its authors predicted that downstaging and improvements in treatment could prevent up to one-third of projected breast cancer deaths over the next decade. “So these are the drivers of populational gain in terms of overall survival – not more drugs, not more services available, but coordination of services and making sure the patient has a right pathway (to diagnosis and treatment),” Dr. Roitberg said.

Dr. Gitlin has received consulting fees from GRAIL LLC, which is a subsidiary of Illumina. Dr. Roitberg has received honoraria from Boehringer Ingelheim, Sanofi, Roche, MSD Oncology, AstraZeneca, Nestle Health Science, Dr Reddy’s, and Oncologia Brazil. He has consulted for MSD Oncology. He has received research funding from Roche, Boehringer Ingelheim, MSD, Bayer, AstraZeneca, and Takeda.

The European Society of Cardiology guidelines on cardiovascular assessment and management of patients undergoing noncardiac surgery have seen extensive revision since the 2014 version.

They still have the same aim – to prevent surgery-related bleeding complications, perioperative myocardial infarction/injury (PMI), stent thrombosis, acute heart failure, arrhythmias, pulmonary embolism, ischemic stroke, and cardiovascular (CV) death.

lyosha_nazarenko/Thinkstock

Cochairpersons Sigrun Halvorsen, MD, PhD, and Julinda Mehilli, MD, presented highlights from the guidelines at the annual congress of the European Society of Cardiology and the document was simultaneously published online in the European Heart Journal.

The document classifies noncardiac surgery into three levels of 30-day risk of CV death, MI, or stroke. Low (< 1%) risk includes eye or thyroid surgery; intermediate (1%-5%) risk includes knee or hip replacement or renal transplant; and high (> 5%) risk includes aortic aneurysm, lung transplant, or pancreatic or bladder cancer surgery (see more examples below).

It classifies patients as low risk if they are younger than 65 without CV disease or CV risk factors (smoking, hypertension, diabetes, dyslipidemia, family history); intermediate risk if they are 65 or older or have CV risk factors; and high risk if they have CVD.  

In an interview, Dr. Halvorsen, professor in cardiology, University of Oslo, zeroed in on three important revisions:

First, recommendations for preoperative ECG and biomarkers are more specific, he noted.

The guidelines advise that before intermediate- or high-risk noncardiac surgery, in patients who have known CVD, CV risk factors (including age 65 or older), or symptoms suggestive of CVD:

• It is recommended to obtain a preoperative 12-lead ECG (class I).
• It is recommended to measure high-sensitivity cardiac troponin T (hs-cTn T) or high-sensitivity cardiac troponin I (hs-cTn I). It is also recommended to measure these biomarkers at 24 hours and 48 hours post surgery (class I).
• It should be considered to measure B-type natriuretic peptide or N-terminal of the prohormone BNP (NT-proBNP).

However, for low-risk patients undergoing low- and intermediate-risk noncardiac surgery, it is not recommended to routinely obtain preoperative ECG, hs-cTn T/I, or BNP/NT-proBNP concentrations (class III).

Troponins have a stronger class I recommendation, compared with the IIA recommendation for BNP, because they are useful for preoperative risk stratification and for diagnosis of PMI, Dr. Halvorsen explained. “Patients receive painkillers after surgery and may have no pain,” she noted, but they may have PMI, which has a bad prognosis.

Second, the guidelines recommend that “all patients should stop smoking 4 weeks before noncardiac surgery [class I],” she noted. Clinicians should also “measure hemoglobin, and if the patient is anemic, treat the anemia.”

Third, the sections on antithrombotic treatment have been significantly revised. “Bridging – stopping an oral antithrombotic drug and switching to a subcutaneous or IV drug – has been common,” Dr. Halvorsen said, “but recently we have new evidence that in most cases that increases the risk of bleeding.”

“We are [now] much more restrictive with respect to bridging” with unfractionated heparin or low-molecular-weight heparin, she said. “We recommend against bridging in patients with low to moderate thrombotic risk,” and bridging should only be considered in patients with mechanical prosthetic heart valves or with very high thrombotic risk.
 

More preoperative recommendations

In the guideline overview session at the congress, Dr. Halverson highlighted some of the new recommendations for preoperative risk assessment.  

If time allows, it is recommended to optimize guideline-recommended treatment of CVD and control of CV risk factors including blood pressure, dyslipidemia, and diabetes, before noncardiac surgery (class I).

Patients commonly have “murmurs, chest pain, dyspnea, and edema that may suggest severe CVD, but may also be caused by noncardiac disease,” she noted. The guidelines state that “for patients with a newly detected murmur and symptoms or signs of CVD, transthoracic echocardiography is recommended before noncardiac surgery (class I).

“Many studies have been performed to try to find out if initiation of specific drugs before surgery could reduce the risk of complications,” Dr. Halvorsen noted. However, few have shown any benefit and “the question of presurgery initiation of beta-blockers has been greatly debated,” she said. “We have again reviewed the literature and concluded ‘Routine initiation of beta-blockers perioperatively is not recommended (class IIIA).’ “

“We adhere to the guidelines on acute and chronic coronary syndrome recommending 6-12 months of dual antiplatelet treatment as a standard before elective surgery,” she said. “However, in case of time-sensitive surgery, the duration of that treatment can be shortened down to a minimum of 1 month after elective PCI and a minimum of 3 months after PCI and ACS.”
 

Patients with specific types of CVD

Dr. Mehilli, a professor at Landshut-Achdorf (Germany) Hospital, highlighted some new guideline recommendations for patients who have specific types of cardiovascular disease.

Coronary artery disease (CAD). “For chronic coronary syndrome, a cardiac workup is recommended only for patients undergoing intermediate risk or high-risk noncardiac surgery.”

“Stress imaging should be considered before any high risk, noncardiac surgery in asymptomatic patients with poor functional capacity and prior PCI or coronary artery bypass graft (new recommendation, class IIa).”

Mitral valve regurgitation. For patients undergoing scheduled noncardiac surgery, who remain symptomatic despite guideline-directed medical treatment for mitral valve regurgitation (including resynchronization and myocardial revascularization), consider a valve intervention – either transcatheter or surgical – before noncardiac surgery in eligible patients with acceptable procedural risk (new recommendation).

Cardiac implantable electronic devices (CIED). For high-risk patients with CIEDs undergoing noncardiac surgery with high probability of electromagnetic interference, a CIED checkup and necessary reprogramming immediately before the procedure should be considered (new recommendation).

Arrhythmias. “I want only to stress,” Dr. Mehilli said, “in patients with atrial fibrillation with acute or worsening hemodynamic instability undergoing noncardiac surgery, an emergency electrical cardioversion is recommended (class I).”

Peripheral artery disease (PAD) and abdominal aortic aneurysm. For these patients “we do not recommend a routine referral for a cardiac workup. But we recommend it for patients with poor functional capacity or with significant risk factors or symptoms (new recommendations).”

Chronic arterial hypertension. “We have modified the recommendation, recommending avoidance of large perioperative fluctuations in blood pressure, and we do not recommend deferring noncardiac surgery in patients with stage 1 or 2 hypertension,” she said.
 

Postoperative cardiovascular complications

The most frequent postoperative cardiovascular complication is PMI, Dr. Mehilli noted.

“In the BASEL-PMI registry, the incidence of this complication around intermediate or high-risk noncardiac surgery was up to 15% among patients older than 65 years or with a history of CAD or PAD, which makes this kind of complication really important to prevent, to assess, and to know how to treat.”

“It is recommended to have a high awareness for perioperative cardiovascular complications, combined with surveillance for PMI in patients undergoing intermediate- or high-risk noncardiac surgery” based on serial measurements of high-sensitivity cardiac troponin.

The guidelines define PMI as “an increase in the delta of high-sensitivity troponin more than the upper level of normal,” Dr. Mehilli said. “It’s different from the one used in a rule-in algorithm for non-STEMI acute coronary syndrome.”

Postoperative atrial fibrillation (AFib) is observed in 2%-30% of noncardiac surgery patients in different registries, particularly in patients undergoing intermediate or high-risk noncardiac surgery, she noted.

“We propose an algorithm on how to prevent and treat this complication. I want to highlight that in patients with hemodynamic unstable postoperative AF[ib], an emergency cardioversion is indicated. For the others, a rate control with the target heart rate of less than 110 beats per minute is indicated.”

In patients with postoperative AFib, long-term oral anticoagulation therapy should be considered in all patients at risk for stroke, considering the anticipated net clinical benefit of oral anticoagulation therapy as well as informed patient preference (new recommendations).

Routine use of beta-blockers to prevent postoperative AFib in patients undergoing noncardiac surgery is not recommended.

The document also covers the management of patients with kidney disease, diabetes, cancer, obesity, and COVID-19. In general, elective noncardiac surgery should be postponed after a patient has COVID-19, until he or she recovers completely, and coexisting conditions are optimized.

The guidelines are available from the ESC website in several formats: pocket guidelines, pocket guidelines smartphone app, guidelines slide set, essential messages, and the European Heart Journal article.
 

Noncardiac surgery risk categories

The guideline includes a table that classifies noncardiac surgeries into three groups, based on the associated 30-day risk of death, MI, or stroke:

• Low (< 1%): breast, dental, eye, thyroid, and minor gynecologic, orthopedic, and urologic surgery.
• Intermediate (1%-5%): carotid surgery, endovascular aortic aneurysm repair, gallbladder surgery, head or neck surgery, hernia repair, peripheral arterial angioplasty, renal transplant, major gynecologic, orthopedic, or neurologic (hip or spine) surgery, or urologic surgery
• High (> 5%): aortic and major vascular surgery (including aortic aneurysm), bladder removal (usually as a result of cancer), limb amputation, lung or liver transplant, pancreatic surgery, or perforated bowel repair.

The guidelines were endorsed by the European Society of Anaesthesiology and Intensive Care. The guideline authors reported numerous disclosures.

A version of this article first appeared on Medscape.com.

The European Society of Cardiology guidelines on cardiovascular assessment and management of patients undergoing noncardiac surgery have seen extensive revision since the 2014 version.

They still have the same aim – to prevent surgery-related bleeding complications, perioperative myocardial infarction/injury (PMI), stent thrombosis, acute heart failure, arrhythmias, pulmonary embolism, ischemic stroke, and cardiovascular (CV) death.

lyosha_nazarenko/Thinkstock

Cochairpersons Sigrun Halvorsen, MD, PhD, and Julinda Mehilli, MD, presented highlights from the guidelines at the annual congress of the European Society of Cardiology and the document was simultaneously published online in the European Heart Journal.

The document classifies noncardiac surgery into three levels of 30-day risk of CV death, MI, or stroke. Low (< 1%) risk includes eye or thyroid surgery; intermediate (1%-5%) risk includes knee or hip replacement or renal transplant; and high (> 5%) risk includes aortic aneurysm, lung transplant, or pancreatic or bladder cancer surgery (see more examples below).

It classifies patients as low risk if they are younger than 65 without CV disease or CV risk factors (smoking, hypertension, diabetes, dyslipidemia, family history); intermediate risk if they are 65 or older or have CV risk factors; and high risk if they have CVD.  

In an interview, Dr. Halvorsen, professor in cardiology, University of Oslo, zeroed in on three important revisions:

First, recommendations for preoperative ECG and biomarkers are more specific, he noted.

The guidelines advise that before intermediate- or high-risk noncardiac surgery, in patients who have known CVD, CV risk factors (including age 65 or older), or symptoms suggestive of CVD:

• It is recommended to obtain a preoperative 12-lead ECG (class I).
• It is recommended to measure high-sensitivity cardiac troponin T (hs-cTn T) or high-sensitivity cardiac troponin I (hs-cTn I). It is also recommended to measure these biomarkers at 24 hours and 48 hours post surgery (class I).
• It should be considered to measure B-type natriuretic peptide or N-terminal of the prohormone BNP (NT-proBNP).

However, for low-risk patients undergoing low- and intermediate-risk noncardiac surgery, it is not recommended to routinely obtain preoperative ECG, hs-cTn T/I, or BNP/NT-proBNP concentrations (class III).

Troponins have a stronger class I recommendation, compared with the IIA recommendation for BNP, because they are useful for preoperative risk stratification and for diagnosis of PMI, Dr. Halvorsen explained. “Patients receive painkillers after surgery and may have no pain,” she noted, but they may have PMI, which has a bad prognosis.

Second, the guidelines recommend that “all patients should stop smoking 4 weeks before noncardiac surgery [class I],” she noted. Clinicians should also “measure hemoglobin, and if the patient is anemic, treat the anemia.”

Third, the sections on antithrombotic treatment have been significantly revised. “Bridging – stopping an oral antithrombotic drug and switching to a subcutaneous or IV drug – has been common,” Dr. Halvorsen said, “but recently we have new evidence that in most cases that increases the risk of bleeding.”

“We are [now] much more restrictive with respect to bridging” with unfractionated heparin or low-molecular-weight heparin, she said. “We recommend against bridging in patients with low to moderate thrombotic risk,” and bridging should only be considered in patients with mechanical prosthetic heart valves or with very high thrombotic risk.
 

More preoperative recommendations

In the guideline overview session at the congress, Dr. Halverson highlighted some of the new recommendations for preoperative risk assessment.  

If time allows, it is recommended to optimize guideline-recommended treatment of CVD and control of CV risk factors including blood pressure, dyslipidemia, and diabetes, before noncardiac surgery (class I).

Patients commonly have “murmurs, chest pain, dyspnea, and edema that may suggest severe CVD, but may also be caused by noncardiac disease,” she noted. The guidelines state that “for patients with a newly detected murmur and symptoms or signs of CVD, transthoracic echocardiography is recommended before noncardiac surgery (class I).

“Many studies have been performed to try to find out if initiation of specific drugs before surgery could reduce the risk of complications,” Dr. Halvorsen noted. However, few have shown any benefit and “the question of presurgery initiation of beta-blockers has been greatly debated,” she said. “We have again reviewed the literature and concluded ‘Routine initiation of beta-blockers perioperatively is not recommended (class IIIA).’ “

“We adhere to the guidelines on acute and chronic coronary syndrome recommending 6-12 months of dual antiplatelet treatment as a standard before elective surgery,” she said. “However, in case of time-sensitive surgery, the duration of that treatment can be shortened down to a minimum of 1 month after elective PCI and a minimum of 3 months after PCI and ACS.”
 

Patients with specific types of CVD

Dr. Mehilli, a professor at Landshut-Achdorf (Germany) Hospital, highlighted some new guideline recommendations for patients who have specific types of cardiovascular disease.

Coronary artery disease (CAD). “For chronic coronary syndrome, a cardiac workup is recommended only for patients undergoing intermediate risk or high-risk noncardiac surgery.”

“Stress imaging should be considered before any high risk, noncardiac surgery in asymptomatic patients with poor functional capacity and prior PCI or coronary artery bypass graft (new recommendation, class IIa).”

Mitral valve regurgitation. For patients undergoing scheduled noncardiac surgery, who remain symptomatic despite guideline-directed medical treatment for mitral valve regurgitation (including resynchronization and myocardial revascularization), consider a valve intervention – either transcatheter or surgical – before noncardiac surgery in eligible patients with acceptable procedural risk (new recommendation).

Cardiac implantable electronic devices (CIED). For high-risk patients with CIEDs undergoing noncardiac surgery with high probability of electromagnetic interference, a CIED checkup and necessary reprogramming immediately before the procedure should be considered (new recommendation).

Arrhythmias. “I want only to stress,” Dr. Mehilli said, “in patients with atrial fibrillation with acute or worsening hemodynamic instability undergoing noncardiac surgery, an emergency electrical cardioversion is recommended (class I).”

Peripheral artery disease (PAD) and abdominal aortic aneurysm. For these patients “we do not recommend a routine referral for a cardiac workup. But we recommend it for patients with poor functional capacity or with significant risk factors or symptoms (new recommendations).”

Chronic arterial hypertension. “We have modified the recommendation, recommending avoidance of large perioperative fluctuations in blood pressure, and we do not recommend deferring noncardiac surgery in patients with stage 1 or 2 hypertension,” she said.
 

Postoperative cardiovascular complications

The most frequent postoperative cardiovascular complication is PMI, Dr. Mehilli noted.

“In the BASEL-PMI registry, the incidence of this complication around intermediate or high-risk noncardiac surgery was up to 15% among patients older than 65 years or with a history of CAD or PAD, which makes this kind of complication really important to prevent, to assess, and to know how to treat.”

“It is recommended to have a high awareness for perioperative cardiovascular complications, combined with surveillance for PMI in patients undergoing intermediate- or high-risk noncardiac surgery” based on serial measurements of high-sensitivity cardiac troponin.

The guidelines define PMI as “an increase in the delta of high-sensitivity troponin more than the upper level of normal,” Dr. Mehilli said. “It’s different from the one used in a rule-in algorithm for non-STEMI acute coronary syndrome.”

Postoperative atrial fibrillation (AFib) is observed in 2%-30% of noncardiac surgery patients in different registries, particularly in patients undergoing intermediate or high-risk noncardiac surgery, she noted.

“We propose an algorithm on how to prevent and treat this complication. I want to highlight that in patients with hemodynamic unstable postoperative AF[ib], an emergency cardioversion is indicated. For the others, a rate control with the target heart rate of less than 110 beats per minute is indicated.”

In patients with postoperative AFib, long-term oral anticoagulation therapy should be considered in all patients at risk for stroke, considering the anticipated net clinical benefit of oral anticoagulation therapy as well as informed patient preference (new recommendations).

Routine use of beta-blockers to prevent postoperative AFib in patients undergoing noncardiac surgery is not recommended.

The document also covers the management of patients with kidney disease, diabetes, cancer, obesity, and COVID-19. In general, elective noncardiac surgery should be postponed after a patient has COVID-19, until he or she recovers completely, and coexisting conditions are optimized.

The guidelines are available from the ESC website in several formats: pocket guidelines, pocket guidelines smartphone app, guidelines slide set, essential messages, and the European Heart Journal article.
 

Noncardiac surgery risk categories

The guideline includes a table that classifies noncardiac surgeries into three groups, based on the associated 30-day risk of death, MI, or stroke:

• Low (< 1%): breast, dental, eye, thyroid, and minor gynecologic, orthopedic, and urologic surgery.
• Intermediate (1%-5%): carotid surgery, endovascular aortic aneurysm repair, gallbladder surgery, head or neck surgery, hernia repair, peripheral arterial angioplasty, renal transplant, major gynecologic, orthopedic, or neurologic (hip or spine) surgery, or urologic surgery
• High (> 5%): aortic and major vascular surgery (including aortic aneurysm), bladder removal (usually as a result of cancer), limb amputation, lung or liver transplant, pancreatic surgery, or perforated bowel repair.

The guidelines were endorsed by the European Society of Anaesthesiology and Intensive Care. The guideline authors reported numerous disclosures.

A version of this article first appeared on Medscape.com.

The European Society of Cardiology guidelines on cardiovascular assessment and management of patients undergoing noncardiac surgery have seen extensive revision since the 2014 version.

They still have the same aim – to prevent surgery-related bleeding complications, perioperative myocardial infarction/injury (PMI), stent thrombosis, acute heart failure, arrhythmias, pulmonary embolism, ischemic stroke, and cardiovascular (CV) death.

lyosha_nazarenko/Thinkstock

Cochairpersons Sigrun Halvorsen, MD, PhD, and Julinda Mehilli, MD, presented highlights from the guidelines at the annual congress of the European Society of Cardiology and the document was simultaneously published online in the European Heart Journal.

The document classifies noncardiac surgery into three levels of 30-day risk of CV death, MI, or stroke. Low (< 1%) risk includes eye or thyroid surgery; intermediate (1%-5%) risk includes knee or hip replacement or renal transplant; and high (> 5%) risk includes aortic aneurysm, lung transplant, or pancreatic or bladder cancer surgery (see more examples below).

It classifies patients as low risk if they are younger than 65 without CV disease or CV risk factors (smoking, hypertension, diabetes, dyslipidemia, family history); intermediate risk if they are 65 or older or have CV risk factors; and high risk if they have CVD.  

In an interview, Dr. Halvorsen, professor in cardiology, University of Oslo, zeroed in on three important revisions:

First, recommendations for preoperative ECG and biomarkers are more specific, he noted.

The guidelines advise that before intermediate- or high-risk noncardiac surgery, in patients who have known CVD, CV risk factors (including age 65 or older), or symptoms suggestive of CVD:

• It is recommended to obtain a preoperative 12-lead ECG (class I).
• It is recommended to measure high-sensitivity cardiac troponin T (hs-cTn T) or high-sensitivity cardiac troponin I (hs-cTn I). It is also recommended to measure these biomarkers at 24 hours and 48 hours post surgery (class I).
• It should be considered to measure B-type natriuretic peptide or N-terminal of the prohormone BNP (NT-proBNP).

However, for low-risk patients undergoing low- and intermediate-risk noncardiac surgery, it is not recommended to routinely obtain preoperative ECG, hs-cTn T/I, or BNP/NT-proBNP concentrations (class III).

Troponins have a stronger class I recommendation, compared with the IIA recommendation for BNP, because they are useful for preoperative risk stratification and for diagnosis of PMI, Dr. Halvorsen explained. “Patients receive painkillers after surgery and may have no pain,” she noted, but they may have PMI, which has a bad prognosis.

Second, the guidelines recommend that “all patients should stop smoking 4 weeks before noncardiac surgery [class I],” she noted. Clinicians should also “measure hemoglobin, and if the patient is anemic, treat the anemia.”

Third, the sections on antithrombotic treatment have been significantly revised. “Bridging – stopping an oral antithrombotic drug and switching to a subcutaneous or IV drug – has been common,” Dr. Halvorsen said, “but recently we have new evidence that in most cases that increases the risk of bleeding.”

“We are [now] much more restrictive with respect to bridging” with unfractionated heparin or low-molecular-weight heparin, she said. “We recommend against bridging in patients with low to moderate thrombotic risk,” and bridging should only be considered in patients with mechanical prosthetic heart valves or with very high thrombotic risk.
 

More preoperative recommendations

In the guideline overview session at the congress, Dr. Halverson highlighted some of the new recommendations for preoperative risk assessment.  

If time allows, it is recommended to optimize guideline-recommended treatment of CVD and control of CV risk factors including blood pressure, dyslipidemia, and diabetes, before noncardiac surgery (class I).

Patients commonly have “murmurs, chest pain, dyspnea, and edema that may suggest severe CVD, but may also be caused by noncardiac disease,” she noted. The guidelines state that “for patients with a newly detected murmur and symptoms or signs of CVD, transthoracic echocardiography is recommended before noncardiac surgery (class I).

“Many studies have been performed to try to find out if initiation of specific drugs before surgery could reduce the risk of complications,” Dr. Halvorsen noted. However, few have shown any benefit and “the question of presurgery initiation of beta-blockers has been greatly debated,” she said. “We have again reviewed the literature and concluded ‘Routine initiation of beta-blockers perioperatively is not recommended (class IIIA).’ “

“We adhere to the guidelines on acute and chronic coronary syndrome recommending 6-12 months of dual antiplatelet treatment as a standard before elective surgery,” she said. “However, in case of time-sensitive surgery, the duration of that treatment can be shortened down to a minimum of 1 month after elective PCI and a minimum of 3 months after PCI and ACS.”
 

Patients with specific types of CVD

Dr. Mehilli, a professor at Landshut-Achdorf (Germany) Hospital, highlighted some new guideline recommendations for patients who have specific types of cardiovascular disease.

Coronary artery disease (CAD). “For chronic coronary syndrome, a cardiac workup is recommended only for patients undergoing intermediate risk or high-risk noncardiac surgery.”

“Stress imaging should be considered before any high risk, noncardiac surgery in asymptomatic patients with poor functional capacity and prior PCI or coronary artery bypass graft (new recommendation, class IIa).”

Mitral valve regurgitation. For patients undergoing scheduled noncardiac surgery, who remain symptomatic despite guideline-directed medical treatment for mitral valve regurgitation (including resynchronization and myocardial revascularization), consider a valve intervention – either transcatheter or surgical – before noncardiac surgery in eligible patients with acceptable procedural risk (new recommendation).

Cardiac implantable electronic devices (CIED). For high-risk patients with CIEDs undergoing noncardiac surgery with high probability of electromagnetic interference, a CIED checkup and necessary reprogramming immediately before the procedure should be considered (new recommendation).

Arrhythmias. “I want only to stress,” Dr. Mehilli said, “in patients with atrial fibrillation with acute or worsening hemodynamic instability undergoing noncardiac surgery, an emergency electrical cardioversion is recommended (class I).”

Peripheral artery disease (PAD) and abdominal aortic aneurysm. For these patients “we do not recommend a routine referral for a cardiac workup. But we recommend it for patients with poor functional capacity or with significant risk factors or symptoms (new recommendations).”

Chronic arterial hypertension. “We have modified the recommendation, recommending avoidance of large perioperative fluctuations in blood pressure, and we do not recommend deferring noncardiac surgery in patients with stage 1 or 2 hypertension,” she said.
 

Postoperative cardiovascular complications

The most frequent postoperative cardiovascular complication is PMI, Dr. Mehilli noted.

“In the BASEL-PMI registry, the incidence of this complication around intermediate or high-risk noncardiac surgery was up to 15% among patients older than 65 years or with a history of CAD or PAD, which makes this kind of complication really important to prevent, to assess, and to know how to treat.”

“It is recommended to have a high awareness for perioperative cardiovascular complications, combined with surveillance for PMI in patients undergoing intermediate- or high-risk noncardiac surgery” based on serial measurements of high-sensitivity cardiac troponin.

The guidelines define PMI as “an increase in the delta of high-sensitivity troponin more than the upper level of normal,” Dr. Mehilli said. “It’s different from the one used in a rule-in algorithm for non-STEMI acute coronary syndrome.”

Postoperative atrial fibrillation (AFib) is observed in 2%-30% of noncardiac surgery patients in different registries, particularly in patients undergoing intermediate or high-risk noncardiac surgery, she noted.

“We propose an algorithm on how to prevent and treat this complication. I want to highlight that in patients with hemodynamic unstable postoperative AF[ib], an emergency cardioversion is indicated. For the others, a rate control with the target heart rate of less than 110 beats per minute is indicated.”

In patients with postoperative AFib, long-term oral anticoagulation therapy should be considered in all patients at risk for stroke, considering the anticipated net clinical benefit of oral anticoagulation therapy as well as informed patient preference (new recommendations).

Routine use of beta-blockers to prevent postoperative AFib in patients undergoing noncardiac surgery is not recommended.

The document also covers the management of patients with kidney disease, diabetes, cancer, obesity, and COVID-19. In general, elective noncardiac surgery should be postponed after a patient has COVID-19, until he or she recovers completely, and coexisting conditions are optimized.

The guidelines are available from the ESC website in several formats: pocket guidelines, pocket guidelines smartphone app, guidelines slide set, essential messages, and the European Heart Journal article.
 

Noncardiac surgery risk categories

The guideline includes a table that classifies noncardiac surgeries into three groups, based on the associated 30-day risk of death, MI, or stroke:

• Low (< 1%): breast, dental, eye, thyroid, and minor gynecologic, orthopedic, and urologic surgery.
• Intermediate (1%-5%): carotid surgery, endovascular aortic aneurysm repair, gallbladder surgery, head or neck surgery, hernia repair, peripheral arterial angioplasty, renal transplant, major gynecologic, orthopedic, or neurologic (hip or spine) surgery, or urologic surgery
• High (> 5%): aortic and major vascular surgery (including aortic aneurysm), bladder removal (usually as a result of cancer), limb amputation, lung or liver transplant, pancreatic surgery, or perforated bowel repair.

The guidelines were endorsed by the European Society of Anaesthesiology and Intensive Care. The guideline authors reported numerous disclosures.

A version of this article first appeared on Medscape.com.

Standing office blood pressure (BP) readings, alone or in combination with seated BP readings, outperform seated BP readings for the initial diagnosis of hypertension, a new study suggests.

Combining three standing and three seated BP measurements in the same visit may lead to a “quicker diagnosis and save people a trip back to the office,” Wanpen Vongpatanasin, MD, professor of internal medicine and director of the hypertension section, cardiology division, UT Southwestern Medical Center, Dallas, said in an interview.

The study was presented at the Hypertension Scientific Sessions, sponsored by the American Heart Association.
 

Practice changing?

Clinical guidelines recommend office BP be taken in a seated position for most patients.

However, research has suggested that the sensitivity of seated office BP in diagnosing hypertension is about 50%, with high specificity around 90% during a single visit, Dr. Vongpatanasin explained.

At the follow-up visit, however, the second office BP yielded higher sensitivity to 80% but specificity fell to 55%. Nevertheless, the accuracy of standing BP measurements for diagnosing hypertension has not been investigated.

In a cross-sectional study, Dr. Vongpatanasin and colleagues determined the accuracy of both seated and standing BP for diagnosing hypertension in a single visit in 125 healthy adults who had not had a previous diagnosis of hypertension and were not taking any BP medications. The cohort had a mean age of 49 years, 62% were women, and 24% were Black.

During each office visit, seated BP was measured three times, then standing BP was measured three times using an automated and validated device.

Average seated BP was 123/76 mm Hg and average standing BP was 126/80 mm Hg.

Of the 125 participants, 42 (34%) had hypertension, defined as 24-hour ambulatory systolic/diastolic BP (SBP/DBP) of ≥ 125/75 mm Hg.

The sensitivity and specificity of seated SBP for hypertension was 43% and 92%, respectively.

“Interestingly, with standing SBP, sensitivity was improved to 74% and specificity dropped to 65% – which is okay; you will have to confirm a positive test anyway and when screening for a common disease you’d rather have a high sensitivity rather than low sensitivity to pick it up in this case,” Dr. Vongpatanasin said.

The area under receiver operating characteristic curve (AUROC) of standing SBP was significantly higher than seated SBP (Bayes factor [BF] = 11.8) when hypertension was defined as 24-hour SBP ≥ 125 mm Hg.

Similarly, when hypertension was defined as 24-hour DBP ≥ 75 mm Hg or daytime DBP ≥ 80 mm Hg, the AUROC of standing DBP was higher than seated DBP (all BF > 3).

The addition of standing to seated BP improved detection of hypertension compared with seated BP alone based on 24-hour SBP/DBP ≥ 125/75 mm Hg or daytime SBP/DBP ≥ 130/80 mm Hg (all BF > 3).

“In our hypertension clinic, we always measure both seated and standing BP in all of our patients,” John Giacona, PA-C, a PhD candidate at UT Southwestern Medical Center and coauthor of the study, told this news organization, 
 

Multiple readings most important

Reached for comment, Johanna Contreras, MD, a cardiologist at Mount Sinai Hospital in New York, noted that diagnosing hypertension is “difficult” and she agrees that multiple readings are important.

“I usually take at least two readings in two different visits before I tell the patient they have high blood pressure,” Dr. Contreras said in an interview.

Dr. Contreras said she takes blood pressure both seated and standing.

“I’m not sure standing versus seated makes a big difference. However, when the patient first comes into the office, it is really important to let them rest and calm down before taking the blood pressure,” she said.

The study had no commercial funding. The authors and Dr. Contreras have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Standing office blood pressure (BP) readings, alone or in combination with seated BP readings, outperform seated BP readings for the initial diagnosis of hypertension, a new study suggests.

Combining three standing and three seated BP measurements in the same visit may lead to a “quicker diagnosis and save people a trip back to the office,” Wanpen Vongpatanasin, MD, professor of internal medicine and director of the hypertension section, cardiology division, UT Southwestern Medical Center, Dallas, said in an interview.

The study was presented at the Hypertension Scientific Sessions, sponsored by the American Heart Association.
 

Practice changing?

Clinical guidelines recommend office BP be taken in a seated position for most patients.

However, research has suggested that the sensitivity of seated office BP in diagnosing hypertension is about 50%, with high specificity around 90% during a single visit, Dr. Vongpatanasin explained.

At the follow-up visit, however, the second office BP yielded higher sensitivity to 80% but specificity fell to 55%. Nevertheless, the accuracy of standing BP measurements for diagnosing hypertension has not been investigated.

In a cross-sectional study, Dr. Vongpatanasin and colleagues determined the accuracy of both seated and standing BP for diagnosing hypertension in a single visit in 125 healthy adults who had not had a previous diagnosis of hypertension and were not taking any BP medications. The cohort had a mean age of 49 years, 62% were women, and 24% were Black.

During each office visit, seated BP was measured three times, then standing BP was measured three times using an automated and validated device.

Average seated BP was 123/76 mm Hg and average standing BP was 126/80 mm Hg.

Of the 125 participants, 42 (34%) had hypertension, defined as 24-hour ambulatory systolic/diastolic BP (SBP/DBP) of ≥ 125/75 mm Hg.

The sensitivity and specificity of seated SBP for hypertension was 43% and 92%, respectively.

“Interestingly, with standing SBP, sensitivity was improved to 74% and specificity dropped to 65% – which is okay; you will have to confirm a positive test anyway and when screening for a common disease you’d rather have a high sensitivity rather than low sensitivity to pick it up in this case,” Dr. Vongpatanasin said.

The area under receiver operating characteristic curve (AUROC) of standing SBP was significantly higher than seated SBP (Bayes factor [BF] = 11.8) when hypertension was defined as 24-hour SBP ≥ 125 mm Hg.

Similarly, when hypertension was defined as 24-hour DBP ≥ 75 mm Hg or daytime DBP ≥ 80 mm Hg, the AUROC of standing DBP was higher than seated DBP (all BF > 3).

The addition of standing to seated BP improved detection of hypertension compared with seated BP alone based on 24-hour SBP/DBP ≥ 125/75 mm Hg or daytime SBP/DBP ≥ 130/80 mm Hg (all BF > 3).

“In our hypertension clinic, we always measure both seated and standing BP in all of our patients,” John Giacona, PA-C, a PhD candidate at UT Southwestern Medical Center and coauthor of the study, told this news organization, 
 

Multiple readings most important

Reached for comment, Johanna Contreras, MD, a cardiologist at Mount Sinai Hospital in New York, noted that diagnosing hypertension is “difficult” and she agrees that multiple readings are important.

“I usually take at least two readings in two different visits before I tell the patient they have high blood pressure,” Dr. Contreras said in an interview.

Dr. Contreras said she takes blood pressure both seated and standing.

“I’m not sure standing versus seated makes a big difference. However, when the patient first comes into the office, it is really important to let them rest and calm down before taking the blood pressure,” she said.

The study had no commercial funding. The authors and Dr. Contreras have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Standing office blood pressure (BP) readings, alone or in combination with seated BP readings, outperform seated BP readings for the initial diagnosis of hypertension, a new study suggests.

Combining three standing and three seated BP measurements in the same visit may lead to a “quicker diagnosis and save people a trip back to the office,” Wanpen Vongpatanasin, MD, professor of internal medicine and director of the hypertension section, cardiology division, UT Southwestern Medical Center, Dallas, said in an interview.

The study was presented at the Hypertension Scientific Sessions, sponsored by the American Heart Association.
 

Practice changing?

Clinical guidelines recommend office BP be taken in a seated position for most patients.

However, research has suggested that the sensitivity of seated office BP in diagnosing hypertension is about 50%, with high specificity around 90% during a single visit, Dr. Vongpatanasin explained.

At the follow-up visit, however, the second office BP yielded higher sensitivity to 80% but specificity fell to 55%. Nevertheless, the accuracy of standing BP measurements for diagnosing hypertension has not been investigated.

In a cross-sectional study, Dr. Vongpatanasin and colleagues determined the accuracy of both seated and standing BP for diagnosing hypertension in a single visit in 125 healthy adults who had not had a previous diagnosis of hypertension and were not taking any BP medications. The cohort had a mean age of 49 years, 62% were women, and 24% were Black.

During each office visit, seated BP was measured three times, then standing BP was measured three times using an automated and validated device.

Average seated BP was 123/76 mm Hg and average standing BP was 126/80 mm Hg.

Of the 125 participants, 42 (34%) had hypertension, defined as 24-hour ambulatory systolic/diastolic BP (SBP/DBP) of ≥ 125/75 mm Hg.

The sensitivity and specificity of seated SBP for hypertension was 43% and 92%, respectively.

“Interestingly, with standing SBP, sensitivity was improved to 74% and specificity dropped to 65% – which is okay; you will have to confirm a positive test anyway and when screening for a common disease you’d rather have a high sensitivity rather than low sensitivity to pick it up in this case,” Dr. Vongpatanasin said.

The area under receiver operating characteristic curve (AUROC) of standing SBP was significantly higher than seated SBP (Bayes factor [BF] = 11.8) when hypertension was defined as 24-hour SBP ≥ 125 mm Hg.

Similarly, when hypertension was defined as 24-hour DBP ≥ 75 mm Hg or daytime DBP ≥ 80 mm Hg, the AUROC of standing DBP was higher than seated DBP (all BF > 3).

The addition of standing to seated BP improved detection of hypertension compared with seated BP alone based on 24-hour SBP/DBP ≥ 125/75 mm Hg or daytime SBP/DBP ≥ 130/80 mm Hg (all BF > 3).

“In our hypertension clinic, we always measure both seated and standing BP in all of our patients,” John Giacona, PA-C, a PhD candidate at UT Southwestern Medical Center and coauthor of the study, told this news organization, 
 

Multiple readings most important

Reached for comment, Johanna Contreras, MD, a cardiologist at Mount Sinai Hospital in New York, noted that diagnosing hypertension is “difficult” and she agrees that multiple readings are important.

“I usually take at least two readings in two different visits before I tell the patient they have high blood pressure,” Dr. Contreras said in an interview.

Dr. Contreras said she takes blood pressure both seated and standing.

“I’m not sure standing versus seated makes a big difference. However, when the patient first comes into the office, it is really important to let them rest and calm down before taking the blood pressure,” she said.

The study had no commercial funding. The authors and Dr. Contreras have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

BARCELONA – A novel “extravascular” implantable cardioverter defibrillator (ICD) that uses substernally placed electrodes surpassed its prespecified efficacy and safety targets in the device’s pivotal trial with 299 patients who received an implant.

The results showed that the extravascular ICD “provides antitachycardia pacing and low energy defibrillation while avoiding the vascular space” for lead placement, Ian Crozier, MD, said at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/MDedge News

“The results are fantastic; they exceeded our expectations,” said Dr. Crozier in an interview, adding that he expects the new device to receive marketing approval from regulatory agencies based on the findings. “This will be the next generation of ICD going forward,” predicted Dr. Crozier, an electrophysiologist cardiologist at Christchurch (New Zealand) Hospital.
 

Moving beyond transvenous and subcutaneous ICDs

Traditional ICDs use transvenous leads, which can cause vascular injury, are prone to lead fracture over time, and can produce serious infections as well as other potential complications. The U.S. Food and Drug Administration first approved an alternative-design, subcutaneous ICD in 2012 that avoids the need for transvenous leads and the risks they pose. But subcutaneous ICDs have their own limitations: an inability to provide antitachycardia pacing or chronic pacing; a limited ability to provide bradycardia pacing; and an increased device size with shorter battery life, because of the high shock power needed for effective performance. These drawbacks have collectively hindered uptake, Dr. Crozier said.

Medtronic

This led to development of the extravascular ICD – 10 years in the making – which uses substernally placed leads that allow antitachycardia pacing and backup pacing in a device with the size of and the anticipated battery longevity of a transvenous ICD device, noted Dr. Crozier.
 

A 98.7% rate of arrhythmia termination at implant

The pivotal trial’s primary efficacy endpoint was successful defibrillation based on terminating an induced, sustained, shockable ventricular arrhythmia at the time of implantation. The rate was 98.7%, compared with a prespecified target of 88%. All patients had a class I or IIa indication for an ICD.

The primary safety endpoint was freedom from major system- or procedure-related complications at 6 months, which occurred at a rate of 92.6%, compared with the study’s prespecified target rate of 79%. Both targets were derived from the historical rates of ICDs with transvenous leads.

Simultaneously with Dr. Crozier’s report at the congress, the results also appeared online in the New England Journal of Medicine.

Although the pivotal study met both prespecified endpoints, the evidence has limitations that make it likely that regulatory bodies will seek additional data, commented Fred Kusumoto, MD, director of heart rhythm services for the Mayo Clinic in Jacksonville, Fla.
 

Short follow-up; questions remain

“Follow-up was relatively short, less than a year,” and “questions remain” about the extravascular ICD’s performance, Dr. Kusumoto said in an interview. “Inappropriate shocks occurred in nearly 10% of patients after 11 month follow-up,” he noted, and also cited the 29 patients who needed revisions including two cases with lead fractures.

“The extravascular lead strategy has an advantage over transvenous systems because of the lower risk for extraction or explant,” and it also provides the antitachycardia pacing that’s not available with subcutaneous ICDs, he granted. But in the new study, antitachycardia termination was delivered to only 10 patients and had “reasonable” effectiveness by resolving 70% of these episodes. “Wide adoption by clinicians will depend on results from larger studies with longer follow-up,” Dr. Kusumoto maintained. He also wanted to see confirmation of the ease of lead removal after longer periods of implantation.

Implantation ‘is not difficult’

The trial ran at 46 sites in 17 countries during September 2019 to October 2021. It enrolled patients with a class I or IIa indication for an ICD, excluding patients with a prior sternotomy or need for chronic pacing, and those unable to undergo defibrillation testing.

Clinicians attempted an implantation in 316 patients and had successful placement in 299 (314 had successful placement of their substernal leads), with 292 having a functional device after 6 months, and 284 completing their planned 6-month follow-up. The median procedure time was 66 minutes, including the time for defibrillation testing.

All of the cardiologists who did the implants had received a full day of training prior to performing the procedure. “This is not a difficult procedure, but it is not a region [the substernal space] that cardiologists are familiar working in,” noted Dr. Crozier, explaining the rationale behind a policy of required implantation training.

Twenty-five adverse events occurred in 23 patients. Eighteen of these events required a system revision, including nine lead dislodgments and five infections. The seven adverse events that did not require a revision included three wound-related episodes and three hospitalizations for inappropriate shock. No patients died, nor were there any cardiac injuries as result of the implant.

During average follow-up of 10.6 months, the implanted devices delivered antitachycardia pacing to 10 patients, successfully terminating 32 of 46 episodes (70%), a rate that Dr. Crozier called “very good, and very comparable to transvenous devices.” The devices also delivered 18 appropriate shocks that successfully converted all 18 episodes.
 

A 10% rate of inappropriate shocks

However, 29 patients (10% of the study cohort) received inappropriate shocks in 81 episodes, with a total of 118 inappropriate shocks delivered, including 34 episodes (42%) triggered by oversensing of a P wave.

“We fully acknowledge that the inappropriate shock rate is higher than what’s seen with transvenous ICDs, but the rate is comparable to what was seen in the early trials with subcutaneous ICDs,” said Dr. Crozier. “We have a number of strategies to reduce the inappropriate shock rate to what we’d expect with conventional devices,” such as making sure that P waves are not detected by the device at the time of implantation, using new algorithms to mitigate P wave sensing, and other programming changes, he added.

Two patients had lead fractures that Dr. Crozier attributed to atypical lead locations and that are likely avoidable in the future. He expressed optimism that the extravascular ICD will avoid the high lead fracture rate over time that remains a problem for ICDs with transvenous leads.

The study also followed a subgroup of 36 patients who underwent a prespecified protocol of chronic defibrillation testing that was successful in all 36.

Dr. Crozier conceded that the extravascular ICD cannot currently deliver chronic pacing, but he expressed optimism that this capability will be available in the future.

“This innovative [extravascular] ICD system would be particularly beneficial for patients with ventricular arrhythmias that can be reliably pace terminated and avoid a transvenous endocardial lead, but more information is required,” concluded Dr. Kusumoto.

The study was sponsored by Medtronic, the company that is developing the extravascular ICD. Dr. Crozier is a consultant to and has received research funding from Medtronic. Dr. Kusumoto had no disclosures.

BARCELONA – A novel “extravascular” implantable cardioverter defibrillator (ICD) that uses substernally placed electrodes surpassed its prespecified efficacy and safety targets in the device’s pivotal trial with 299 patients who received an implant.

The results showed that the extravascular ICD “provides antitachycardia pacing and low energy defibrillation while avoiding the vascular space” for lead placement, Ian Crozier, MD, said at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/MDedge News

“The results are fantastic; they exceeded our expectations,” said Dr. Crozier in an interview, adding that he expects the new device to receive marketing approval from regulatory agencies based on the findings. “This will be the next generation of ICD going forward,” predicted Dr. Crozier, an electrophysiologist cardiologist at Christchurch (New Zealand) Hospital.
 

Moving beyond transvenous and subcutaneous ICDs

Traditional ICDs use transvenous leads, which can cause vascular injury, are prone to lead fracture over time, and can produce serious infections as well as other potential complications. The U.S. Food and Drug Administration first approved an alternative-design, subcutaneous ICD in 2012 that avoids the need for transvenous leads and the risks they pose. But subcutaneous ICDs have their own limitations: an inability to provide antitachycardia pacing or chronic pacing; a limited ability to provide bradycardia pacing; and an increased device size with shorter battery life, because of the high shock power needed for effective performance. These drawbacks have collectively hindered uptake, Dr. Crozier said.

Medtronic

This led to development of the extravascular ICD – 10 years in the making – which uses substernally placed leads that allow antitachycardia pacing and backup pacing in a device with the size of and the anticipated battery longevity of a transvenous ICD device, noted Dr. Crozier.
 

A 98.7% rate of arrhythmia termination at implant

The pivotal trial’s primary efficacy endpoint was successful defibrillation based on terminating an induced, sustained, shockable ventricular arrhythmia at the time of implantation. The rate was 98.7%, compared with a prespecified target of 88%. All patients had a class I or IIa indication for an ICD.

The primary safety endpoint was freedom from major system- or procedure-related complications at 6 months, which occurred at a rate of 92.6%, compared with the study’s prespecified target rate of 79%. Both targets were derived from the historical rates of ICDs with transvenous leads.

Simultaneously with Dr. Crozier’s report at the congress, the results also appeared online in the New England Journal of Medicine.

Although the pivotal study met both prespecified endpoints, the evidence has limitations that make it likely that regulatory bodies will seek additional data, commented Fred Kusumoto, MD, director of heart rhythm services for the Mayo Clinic in Jacksonville, Fla.
 

Short follow-up; questions remain

“Follow-up was relatively short, less than a year,” and “questions remain” about the extravascular ICD’s performance, Dr. Kusumoto said in an interview. “Inappropriate shocks occurred in nearly 10% of patients after 11 month follow-up,” he noted, and also cited the 29 patients who needed revisions including two cases with lead fractures.

“The extravascular lead strategy has an advantage over transvenous systems because of the lower risk for extraction or explant,” and it also provides the antitachycardia pacing that’s not available with subcutaneous ICDs, he granted. But in the new study, antitachycardia termination was delivered to only 10 patients and had “reasonable” effectiveness by resolving 70% of these episodes. “Wide adoption by clinicians will depend on results from larger studies with longer follow-up,” Dr. Kusumoto maintained. He also wanted to see confirmation of the ease of lead removal after longer periods of implantation.

Implantation ‘is not difficult’

The trial ran at 46 sites in 17 countries during September 2019 to October 2021. It enrolled patients with a class I or IIa indication for an ICD, excluding patients with a prior sternotomy or need for chronic pacing, and those unable to undergo defibrillation testing.

Clinicians attempted an implantation in 316 patients and had successful placement in 299 (314 had successful placement of their substernal leads), with 292 having a functional device after 6 months, and 284 completing their planned 6-month follow-up. The median procedure time was 66 minutes, including the time for defibrillation testing.

All of the cardiologists who did the implants had received a full day of training prior to performing the procedure. “This is not a difficult procedure, but it is not a region [the substernal space] that cardiologists are familiar working in,” noted Dr. Crozier, explaining the rationale behind a policy of required implantation training.

Twenty-five adverse events occurred in 23 patients. Eighteen of these events required a system revision, including nine lead dislodgments and five infections. The seven adverse events that did not require a revision included three wound-related episodes and three hospitalizations for inappropriate shock. No patients died, nor were there any cardiac injuries as result of the implant.

During average follow-up of 10.6 months, the implanted devices delivered antitachycardia pacing to 10 patients, successfully terminating 32 of 46 episodes (70%), a rate that Dr. Crozier called “very good, and very comparable to transvenous devices.” The devices also delivered 18 appropriate shocks that successfully converted all 18 episodes.
 

A 10% rate of inappropriate shocks

However, 29 patients (10% of the study cohort) received inappropriate shocks in 81 episodes, with a total of 118 inappropriate shocks delivered, including 34 episodes (42%) triggered by oversensing of a P wave.

“We fully acknowledge that the inappropriate shock rate is higher than what’s seen with transvenous ICDs, but the rate is comparable to what was seen in the early trials with subcutaneous ICDs,” said Dr. Crozier. “We have a number of strategies to reduce the inappropriate shock rate to what we’d expect with conventional devices,” such as making sure that P waves are not detected by the device at the time of implantation, using new algorithms to mitigate P wave sensing, and other programming changes, he added.

Two patients had lead fractures that Dr. Crozier attributed to atypical lead locations and that are likely avoidable in the future. He expressed optimism that the extravascular ICD will avoid the high lead fracture rate over time that remains a problem for ICDs with transvenous leads.

The study also followed a subgroup of 36 patients who underwent a prespecified protocol of chronic defibrillation testing that was successful in all 36.

Dr. Crozier conceded that the extravascular ICD cannot currently deliver chronic pacing, but he expressed optimism that this capability will be available in the future.

“This innovative [extravascular] ICD system would be particularly beneficial for patients with ventricular arrhythmias that can be reliably pace terminated and avoid a transvenous endocardial lead, but more information is required,” concluded Dr. Kusumoto.

The study was sponsored by Medtronic, the company that is developing the extravascular ICD. Dr. Crozier is a consultant to and has received research funding from Medtronic. Dr. Kusumoto had no disclosures.

BARCELONA – A novel “extravascular” implantable cardioverter defibrillator (ICD) that uses substernally placed electrodes surpassed its prespecified efficacy and safety targets in the device’s pivotal trial with 299 patients who received an implant.

The results showed that the extravascular ICD “provides antitachycardia pacing and low energy defibrillation while avoiding the vascular space” for lead placement, Ian Crozier, MD, said at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/MDedge News

“The results are fantastic; they exceeded our expectations,” said Dr. Crozier in an interview, adding that he expects the new device to receive marketing approval from regulatory agencies based on the findings. “This will be the next generation of ICD going forward,” predicted Dr. Crozier, an electrophysiologist cardiologist at Christchurch (New Zealand) Hospital.
 

Moving beyond transvenous and subcutaneous ICDs

Traditional ICDs use transvenous leads, which can cause vascular injury, are prone to lead fracture over time, and can produce serious infections as well as other potential complications. The U.S. Food and Drug Administration first approved an alternative-design, subcutaneous ICD in 2012 that avoids the need for transvenous leads and the risks they pose. But subcutaneous ICDs have their own limitations: an inability to provide antitachycardia pacing or chronic pacing; a limited ability to provide bradycardia pacing; and an increased device size with shorter battery life, because of the high shock power needed for effective performance. These drawbacks have collectively hindered uptake, Dr. Crozier said.

Medtronic

This led to development of the extravascular ICD – 10 years in the making – which uses substernally placed leads that allow antitachycardia pacing and backup pacing in a device with the size of and the anticipated battery longevity of a transvenous ICD device, noted Dr. Crozier.
 

A 98.7% rate of arrhythmia termination at implant

The pivotal trial’s primary efficacy endpoint was successful defibrillation based on terminating an induced, sustained, shockable ventricular arrhythmia at the time of implantation. The rate was 98.7%, compared with a prespecified target of 88%. All patients had a class I or IIa indication for an ICD.

The primary safety endpoint was freedom from major system- or procedure-related complications at 6 months, which occurred at a rate of 92.6%, compared with the study’s prespecified target rate of 79%. Both targets were derived from the historical rates of ICDs with transvenous leads.

Simultaneously with Dr. Crozier’s report at the congress, the results also appeared online in the New England Journal of Medicine.

Although the pivotal study met both prespecified endpoints, the evidence has limitations that make it likely that regulatory bodies will seek additional data, commented Fred Kusumoto, MD, director of heart rhythm services for the Mayo Clinic in Jacksonville, Fla.
 

Short follow-up; questions remain

“Follow-up was relatively short, less than a year,” and “questions remain” about the extravascular ICD’s performance, Dr. Kusumoto said in an interview. “Inappropriate shocks occurred in nearly 10% of patients after 11 month follow-up,” he noted, and also cited the 29 patients who needed revisions including two cases with lead fractures.

“The extravascular lead strategy has an advantage over transvenous systems because of the lower risk for extraction or explant,” and it also provides the antitachycardia pacing that’s not available with subcutaneous ICDs, he granted. But in the new study, antitachycardia termination was delivered to only 10 patients and had “reasonable” effectiveness by resolving 70% of these episodes. “Wide adoption by clinicians will depend on results from larger studies with longer follow-up,” Dr. Kusumoto maintained. He also wanted to see confirmation of the ease of lead removal after longer periods of implantation.

Implantation ‘is not difficult’

The trial ran at 46 sites in 17 countries during September 2019 to October 2021. It enrolled patients with a class I or IIa indication for an ICD, excluding patients with a prior sternotomy or need for chronic pacing, and those unable to undergo defibrillation testing.

Clinicians attempted an implantation in 316 patients and had successful placement in 299 (314 had successful placement of their substernal leads), with 292 having a functional device after 6 months, and 284 completing their planned 6-month follow-up. The median procedure time was 66 minutes, including the time for defibrillation testing.

All of the cardiologists who did the implants had received a full day of training prior to performing the procedure. “This is not a difficult procedure, but it is not a region [the substernal space] that cardiologists are familiar working in,” noted Dr. Crozier, explaining the rationale behind a policy of required implantation training.

Twenty-five adverse events occurred in 23 patients. Eighteen of these events required a system revision, including nine lead dislodgments and five infections. The seven adverse events that did not require a revision included three wound-related episodes and three hospitalizations for inappropriate shock. No patients died, nor were there any cardiac injuries as result of the implant.

During average follow-up of 10.6 months, the implanted devices delivered antitachycardia pacing to 10 patients, successfully terminating 32 of 46 episodes (70%), a rate that Dr. Crozier called “very good, and very comparable to transvenous devices.” The devices also delivered 18 appropriate shocks that successfully converted all 18 episodes.
 

A 10% rate of inappropriate shocks

However, 29 patients (10% of the study cohort) received inappropriate shocks in 81 episodes, with a total of 118 inappropriate shocks delivered, including 34 episodes (42%) triggered by oversensing of a P wave.

“We fully acknowledge that the inappropriate shock rate is higher than what’s seen with transvenous ICDs, but the rate is comparable to what was seen in the early trials with subcutaneous ICDs,” said Dr. Crozier. “We have a number of strategies to reduce the inappropriate shock rate to what we’d expect with conventional devices,” such as making sure that P waves are not detected by the device at the time of implantation, using new algorithms to mitigate P wave sensing, and other programming changes, he added.

Two patients had lead fractures that Dr. Crozier attributed to atypical lead locations and that are likely avoidable in the future. He expressed optimism that the extravascular ICD will avoid the high lead fracture rate over time that remains a problem for ICDs with transvenous leads.

The study also followed a subgroup of 36 patients who underwent a prespecified protocol of chronic defibrillation testing that was successful in all 36.

Dr. Crozier conceded that the extravascular ICD cannot currently deliver chronic pacing, but he expressed optimism that this capability will be available in the future.

“This innovative [extravascular] ICD system would be particularly beneficial for patients with ventricular arrhythmias that can be reliably pace terminated and avoid a transvenous endocardial lead, but more information is required,” concluded Dr. Kusumoto.

The study was sponsored by Medtronic, the company that is developing the extravascular ICD. Dr. Crozier is a consultant to and has received research funding from Medtronic. Dr. Kusumoto had no disclosures.

MILAN – The day after deucravacitinib became the first TYK2 inhibitor approved for the treatment of moderate to severe psoriasis, long-term data were presented at the annual congress of the European Academy of Dermatology and Venereology, suggesting that a high degree of benefit persists for at least 2 years, making this oral drug a potential competitor for biologics.

As a once-daily drug, deucravacitinib has “the potential to be a treatment of choice and a new standard of care for patients who require systemic therapy for their moderate to severe plaque psoriasis,” said Mark G. Lebwohl, MD, professor of dermatology and dean of clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York.

Just 2 months after the 52-week data from the phase 3 POETYK PSO-1 trial were published online in the Journal of the American Academy of Dermatology, a long-term extension study found essentially no loss of benefit at 112 weeks, according to Dr. Lebwohl.

One of the two co-primary endpoints was a 75% clearance on the Psoriasis and Severity Index (PASI75) score. At 52 weeks, 80.2% of patients on deucravacitinib had met this criterion of benefit. At 112 weeks, the proportion was 84.4%.

The other primary endpoint was a static Physician’s Global Assessment (sPGA) score of clear or almost clear skin. The proportion of patients meeting this criterion at weeks 52 and 112 weeks were 65.6% and 67.6%, respectively.

When assessed by Treatment Failure Rule (TFR) or modified nonresponder imputation (mNRI), results were similar. For both, the primary endpoints at every time interval were just one or two percentage points lower but not clinically meaningfully different, according to Dr. Lebwohl.

The same type of sustained response out to 112 weeks was observed in multiple analyses. When the researchers isolated the subgroup of patients who had achieved a PASI 75 response at 16 weeks (100%), there was a modest decline in the PASI 75 rate at week 52 (90.2%) but then no additional decline at week 112 (91.3%).

There were essentially no changes in the PASI 90 rates at week 16 (63%), week 52 (65.3%), and week 112 (63.1%), Dr. Lebwohl reported. PASI 100 rates, once achieved, were sustained long term.

The target, TYK2, is one of four Janus kinase (JAK) inhibitors. Until now, almost all JAK inhibitors have had greater relative specificity for JAK 1, JAK 2, and JAK 3, but several inhibitors of TYK2 inhibitors other than deucravacitinib are in development for inflammatory diseases. Deucravacitinib (Sotyktu), approved by the Food and Drug Administration on Sept. 9, is the only TYK2 inhibitor with regulatory approval for plaque psoriasis.

In the POETYK PSO-1 trial, 666 patients were initially randomized in a 2:1:1 ratio to 6 mg deucravacitinib (now the approved dose), placebo, or the oral phosphodiesterase 4 inhibitor apremilast. At week 16, patients on placebo were switched over to deucravacitinib. At week 24, patients who did not achieve a PASI 50 on apremilast (which had been titrated to 10 mg daily to 30 mg twice a day over the first 5 days of dosing) were switched to deucravacitinib.

In the previously reported data, deucravacitinib was superior for all efficacy endpoints at week 16, including an analysis of quality of life when compared with placebo (P < .0001) or apremilast (P = .0088). At week 52, after having been switched to deucravacitinib at week 16, patients on placebo achieved comparable responses on the efficacy measures in this study, including PASI75.

Relative to JAK inhibitors commonly used in rheumatoid arthritis and other inflammatory diseases, the greater specificity of deucravacitinib for TYK2 appears to have meaningful safety advantages, according to Dr. Lebwohl. Targeted mostly on the TYK2 regulatory domain, deucravacitinib largely avoids inhibition of the JAK 1, 2, and 3 subtypes. Dr. Lebwohl said this explains why deucravacitinib labeling does not share the boxed warnings about off-target effects, such as those on the cardiovascular system, that can be found in the labeling of other JAK inhibitors.

In the published 52-week data, the discontinuation rate for adverse events was lower in the group randomized to deucravacitinib arm than in the placebo arm. In the extended follow-up, there were no new signals for adverse events, including those involving the CV system or immune function.

The key message so far from the long-term follow-up, which is ongoing, is that “continuous treatment with deucravacitinib is associated with durable efficacy,” Dr. Lebwohl said. It is this combination of sustained efficacy and safety that led Dr. Lebwohl to suggest it as a reasonable oral competitor to injectable biologics.

“Patients now have a choice,” he said.

Jashin J. Wu, MD, a board member of the National Psoriasis Foundation and an associate professor in the department of dermatology, University of Miami, has been following the development of deucravacitinib. He said that the recent FDA approval validates the clinical evidence of benefit and safety, while the long-term data presented at the EADV congress support its role in expanding treatment options.

“Deucravacitinib is a very effective oral agent for moderate to severe plaque psoriasis with strong maintenance of effect through week 112,” he said. Differentiating it from other JAK inhibitors, the FDA approval “confirms the safety of this agent as there is no boxed warning,” he added.

Dr. Lebwohl reports financial relationships with more than 30 pharmaceutical companies, including Bristol-Myers Squibb, the manufacturer of deucravacitinib. Dr. Wu has financial relationships with 14 pharmaceutical companies, including Bristol-Myers Squibb, but he was not an investigator for the phase 3 trials of deucravacitinib.

MILAN – The day after deucravacitinib became the first TYK2 inhibitor approved for the treatment of moderate to severe psoriasis, long-term data were presented at the annual congress of the European Academy of Dermatology and Venereology, suggesting that a high degree of benefit persists for at least 2 years, making this oral drug a potential competitor for biologics.

As a once-daily drug, deucravacitinib has “the potential to be a treatment of choice and a new standard of care for patients who require systemic therapy for their moderate to severe plaque psoriasis,” said Mark G. Lebwohl, MD, professor of dermatology and dean of clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York.

Just 2 months after the 52-week data from the phase 3 POETYK PSO-1 trial were published online in the Journal of the American Academy of Dermatology, a long-term extension study found essentially no loss of benefit at 112 weeks, according to Dr. Lebwohl.

One of the two co-primary endpoints was a 75% clearance on the Psoriasis and Severity Index (PASI75) score. At 52 weeks, 80.2% of patients on deucravacitinib had met this criterion of benefit. At 112 weeks, the proportion was 84.4%.

The other primary endpoint was a static Physician’s Global Assessment (sPGA) score of clear or almost clear skin. The proportion of patients meeting this criterion at weeks 52 and 112 weeks were 65.6% and 67.6%, respectively.

When assessed by Treatment Failure Rule (TFR) or modified nonresponder imputation (mNRI), results were similar. For both, the primary endpoints at every time interval were just one or two percentage points lower but not clinically meaningfully different, according to Dr. Lebwohl.

The same type of sustained response out to 112 weeks was observed in multiple analyses. When the researchers isolated the subgroup of patients who had achieved a PASI 75 response at 16 weeks (100%), there was a modest decline in the PASI 75 rate at week 52 (90.2%) but then no additional decline at week 112 (91.3%).

There were essentially no changes in the PASI 90 rates at week 16 (63%), week 52 (65.3%), and week 112 (63.1%), Dr. Lebwohl reported. PASI 100 rates, once achieved, were sustained long term.

The target, TYK2, is one of four Janus kinase (JAK) inhibitors. Until now, almost all JAK inhibitors have had greater relative specificity for JAK 1, JAK 2, and JAK 3, but several inhibitors of TYK2 inhibitors other than deucravacitinib are in development for inflammatory diseases. Deucravacitinib (Sotyktu), approved by the Food and Drug Administration on Sept. 9, is the only TYK2 inhibitor with regulatory approval for plaque psoriasis.

In the POETYK PSO-1 trial, 666 patients were initially randomized in a 2:1:1 ratio to 6 mg deucravacitinib (now the approved dose), placebo, or the oral phosphodiesterase 4 inhibitor apremilast. At week 16, patients on placebo were switched over to deucravacitinib. At week 24, patients who did not achieve a PASI 50 on apremilast (which had been titrated to 10 mg daily to 30 mg twice a day over the first 5 days of dosing) were switched to deucravacitinib.

In the previously reported data, deucravacitinib was superior for all efficacy endpoints at week 16, including an analysis of quality of life when compared with placebo (P < .0001) or apremilast (P = .0088). At week 52, after having been switched to deucravacitinib at week 16, patients on placebo achieved comparable responses on the efficacy measures in this study, including PASI75.

Relative to JAK inhibitors commonly used in rheumatoid arthritis and other inflammatory diseases, the greater specificity of deucravacitinib for TYK2 appears to have meaningful safety advantages, according to Dr. Lebwohl. Targeted mostly on the TYK2 regulatory domain, deucravacitinib largely avoids inhibition of the JAK 1, 2, and 3 subtypes. Dr. Lebwohl said this explains why deucravacitinib labeling does not share the boxed warnings about off-target effects, such as those on the cardiovascular system, that can be found in the labeling of other JAK inhibitors.

In the published 52-week data, the discontinuation rate for adverse events was lower in the group randomized to deucravacitinib arm than in the placebo arm. In the extended follow-up, there were no new signals for adverse events, including those involving the CV system or immune function.

The key message so far from the long-term follow-up, which is ongoing, is that “continuous treatment with deucravacitinib is associated with durable efficacy,” Dr. Lebwohl said. It is this combination of sustained efficacy and safety that led Dr. Lebwohl to suggest it as a reasonable oral competitor to injectable biologics.

“Patients now have a choice,” he said.

Jashin J. Wu, MD, a board member of the National Psoriasis Foundation and an associate professor in the department of dermatology, University of Miami, has been following the development of deucravacitinib. He said that the recent FDA approval validates the clinical evidence of benefit and safety, while the long-term data presented at the EADV congress support its role in expanding treatment options.

“Deucravacitinib is a very effective oral agent for moderate to severe plaque psoriasis with strong maintenance of effect through week 112,” he said. Differentiating it from other JAK inhibitors, the FDA approval “confirms the safety of this agent as there is no boxed warning,” he added.

Dr. Lebwohl reports financial relationships with more than 30 pharmaceutical companies, including Bristol-Myers Squibb, the manufacturer of deucravacitinib. Dr. Wu has financial relationships with 14 pharmaceutical companies, including Bristol-Myers Squibb, but he was not an investigator for the phase 3 trials of deucravacitinib.

MILAN – The day after deucravacitinib became the first TYK2 inhibitor approved for the treatment of moderate to severe psoriasis, long-term data were presented at the annual congress of the European Academy of Dermatology and Venereology, suggesting that a high degree of benefit persists for at least 2 years, making this oral drug a potential competitor for biologics.

As a once-daily drug, deucravacitinib has “the potential to be a treatment of choice and a new standard of care for patients who require systemic therapy for their moderate to severe plaque psoriasis,” said Mark G. Lebwohl, MD, professor of dermatology and dean of clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York.

Just 2 months after the 52-week data from the phase 3 POETYK PSO-1 trial were published online in the Journal of the American Academy of Dermatology, a long-term extension study found essentially no loss of benefit at 112 weeks, according to Dr. Lebwohl.

One of the two co-primary endpoints was a 75% clearance on the Psoriasis and Severity Index (PASI75) score. At 52 weeks, 80.2% of patients on deucravacitinib had met this criterion of benefit. At 112 weeks, the proportion was 84.4%.

The other primary endpoint was a static Physician’s Global Assessment (sPGA) score of clear or almost clear skin. The proportion of patients meeting this criterion at weeks 52 and 112 weeks were 65.6% and 67.6%, respectively.

When assessed by Treatment Failure Rule (TFR) or modified nonresponder imputation (mNRI), results were similar. For both, the primary endpoints at every time interval were just one or two percentage points lower but not clinically meaningfully different, according to Dr. Lebwohl.

The same type of sustained response out to 112 weeks was observed in multiple analyses. When the researchers isolated the subgroup of patients who had achieved a PASI 75 response at 16 weeks (100%), there was a modest decline in the PASI 75 rate at week 52 (90.2%) but then no additional decline at week 112 (91.3%).

There were essentially no changes in the PASI 90 rates at week 16 (63%), week 52 (65.3%), and week 112 (63.1%), Dr. Lebwohl reported. PASI 100 rates, once achieved, were sustained long term.

The target, TYK2, is one of four Janus kinase (JAK) inhibitors. Until now, almost all JAK inhibitors have had greater relative specificity for JAK 1, JAK 2, and JAK 3, but several inhibitors of TYK2 inhibitors other than deucravacitinib are in development for inflammatory diseases. Deucravacitinib (Sotyktu), approved by the Food and Drug Administration on Sept. 9, is the only TYK2 inhibitor with regulatory approval for plaque psoriasis.

In the POETYK PSO-1 trial, 666 patients were initially randomized in a 2:1:1 ratio to 6 mg deucravacitinib (now the approved dose), placebo, or the oral phosphodiesterase 4 inhibitor apremilast. At week 16, patients on placebo were switched over to deucravacitinib. At week 24, patients who did not achieve a PASI 50 on apremilast (which had been titrated to 10 mg daily to 30 mg twice a day over the first 5 days of dosing) were switched to deucravacitinib.

In the previously reported data, deucravacitinib was superior for all efficacy endpoints at week 16, including an analysis of quality of life when compared with placebo (P < .0001) or apremilast (P = .0088). At week 52, after having been switched to deucravacitinib at week 16, patients on placebo achieved comparable responses on the efficacy measures in this study, including PASI75.

Relative to JAK inhibitors commonly used in rheumatoid arthritis and other inflammatory diseases, the greater specificity of deucravacitinib for TYK2 appears to have meaningful safety advantages, according to Dr. Lebwohl. Targeted mostly on the TYK2 regulatory domain, deucravacitinib largely avoids inhibition of the JAK 1, 2, and 3 subtypes. Dr. Lebwohl said this explains why deucravacitinib labeling does not share the boxed warnings about off-target effects, such as those on the cardiovascular system, that can be found in the labeling of other JAK inhibitors.

In the published 52-week data, the discontinuation rate for adverse events was lower in the group randomized to deucravacitinib arm than in the placebo arm. In the extended follow-up, there were no new signals for adverse events, including those involving the CV system or immune function.

The key message so far from the long-term follow-up, which is ongoing, is that “continuous treatment with deucravacitinib is associated with durable efficacy,” Dr. Lebwohl said. It is this combination of sustained efficacy and safety that led Dr. Lebwohl to suggest it as a reasonable oral competitor to injectable biologics.

“Patients now have a choice,” he said.

Jashin J. Wu, MD, a board member of the National Psoriasis Foundation and an associate professor in the department of dermatology, University of Miami, has been following the development of deucravacitinib. He said that the recent FDA approval validates the clinical evidence of benefit and safety, while the long-term data presented at the EADV congress support its role in expanding treatment options.

“Deucravacitinib is a very effective oral agent for moderate to severe plaque psoriasis with strong maintenance of effect through week 112,” he said. Differentiating it from other JAK inhibitors, the FDA approval “confirms the safety of this agent as there is no boxed warning,” he added.

Dr. Lebwohl reports financial relationships with more than 30 pharmaceutical companies, including Bristol-Myers Squibb, the manufacturer of deucravacitinib. Dr. Wu has financial relationships with 14 pharmaceutical companies, including Bristol-Myers Squibb, but he was not an investigator for the phase 3 trials of deucravacitinib.